Trigger 9 - Epigenetics and Lung cancer Flashcards
(223 cards)
1
Q
Define Epigenetics
A
Epigenetics refers to the modifications to DNA which alter how the DNA is used, but do not alter the underlying genetic sequence.
2
Q
What factors can alter epigenetics?
A) Genetic mutations
B) Environmental factors
C) Physical exercise
D) All of the above
A
B) Environmental factors
3
Q
DNA methylation involves the addition of a ____ group to cytosine residues in the DNA sequence.
A
methyl (CH3)
4
Q
True or False:
CpG sites are distributed equally across the genome.
A
False
5
Q
Describe Tissue Specificity of DNAm Patterns
A
DNA methylation has tissue and cell-specific patterns at certain CpG sites. This can confound results of research studies if not accounted for. During study design, it’s critical to consider disease-relevant tissues/cells.
6
Q
Which of the following is enriched in regulatory elements and clusters CpG sites?
A) CpG islands
B) Tandem repeats
C) Telomeres
D) Introns
A
A) CpG islands
7
Q
CpG sites cluster in CpG-rich regions called ___.
A
CpG islands
8
Q
True or False:
DNA methylation patterns are consistent across all tissues and cells.
A
False
9
Q
Define DNAm
A
DNA methylation involves the addition of a methyl group (CH3) to cytosine residues in the DNA sequence.
10
Q
How many DNAm-based assays are available to predict treatment response?
A) One
B) Three
C) Five
D) Ten
A
C) Five
11
Q
Understanding subtype informs ___ and ___ strategy.
A
prognosis; treatment
12
Q
True or False:
Assays for prediction of treatment response using DNAm always involve tumor biopsies.
A
True
13
Q
Define DNA Methylation
A
DNA methylation involves the addition of a methyl group (CH3) to cytosine residues in the DNA sequence.
14
Q
Where does the majority of DNA methylation (DNAm) occur?
A) Adenine residues
B) Guanine residues
C) Thymine residues
D) Cytosine residues
A
D) Cytosine residues
15
Q
CpG sites are not distributed equally across the ____.
A
genome
16
Q
True or False:
CpG islands are CpG-poor regions.
A
False
17
Q
Describe Tissue Specificity of DNAm Patterns
A
DNA methylation exhibits tissue and cell-specific patterns at certain CpG sites. Failure to account for this specificity can lead to skewed research results. Researchers must consider disease-relevant tissues/cells during study design.
18
Q
Which of the following factors can DNA methylation patterns be altered by?
A) Moon phases
B) Solar flares
C) Environmental factors
D) Time of day
A
C) Environmental factors
19
Q
DNA methylation has tissue and ____ specific patterns at certain CpG sites.
A
cell
20
Q
True or False:
Understanding subtype does not impact prognosis or treatment strategy.
A
False
21
Q
Define Personalized Medicine:
A
Personalized medicine involves tailoring medical treatment to the individual characteristics of each patient.
22
Q
What is the Heidelberg classifier used for?
A) Identifying plant species
B) Predicting response to cancer treatment
C) Determining blood type
D) Predicting weather patterns
A
B) Predicting response to cancer treatment
23
Q
True or False:
DNAm-based assays for predicting treatment response never require tumor biopsies.
A
False
24
Q
Define MGMT:
A
MGMT is a DNA repair enzyme whose methylation status in glioblastoma tumors predicts a favorable response to alkylating agents such as carmustine/BCNU or temozolomide.
25
What type of tumors is MGMT promoter methylation status recommended to be tested in according to NCCN guidelines?
A) Grade 1/2 gliomas
B) Grade 3/4 gliomas
C) Breast tumors
D) Lung tumors
B) Grade 3/4 gliomas
26
MGMT methylation status in glioblastoma tumors predicts a favorable response to ____ agents.
alkylating
27
True or False:
MGMT methylation status is not associated with response to alkylating agents.
False
28
Describe PITX2
PITX2 methylation status in breast cancer tumors predicts response to adjuvant anthracycline-based chemotherapy in patients with high-risk breast cancer. It has also been shown to predict the risk of distant metastases in breast cancer. PITX2 is a transcription factor involved in pituitary-specific gene regulation and left-right patterning in embryonic and organogenic development.
29
Which type of chemotherapy does PITX2 methylation status predict response to in breast cancer?
A) Platinum-based
B) Taxane-based
C) Anthracycline-based
D) Antimetabolite-based
C) Anthracycline-based
30
One CE-marked test available for PITX2 methylation status is the Therascreen PITX2 RGQ PCR assay from ___.
Qiagen
31
Define Epi-ASCENT Project
The Epi-ASCENT project aims to identify DNA methylation signatures of aggression and indolence in LDCT-detected lung cancers by comparing fast and slow-growing tumors identified as part of the ASCENT study.
32
What is the main objective of the ASCENT study?
A) To analyze molecular and cellular signatures of breast cancer
B) To assess if low dose CT scans could improve early detection of lung cancers
C) To investigate the efficacy of chemotherapy in treating lung cancer
D) To study the effects of smoking on lung health
B) To assess if low dose CT scans could improve early detection of lung cancers
33
The SUMMIT study, established in 2017, aimed to assess if low dose CT scans could improve early detection of lung cancers. The ASCENT study, established in 2020, aims to analyze the molecular and cellular signatures of ____-detected lung cancers.
screen
34
True or False:
The Epi-ASCENT study aims to identify DNA methylation signatures of aggression and indolence in LDCT-detected lung cancers.
True
35
Describe Epi-ASCENT Projec
The Epi-ASCENT project aims to identify DNA methylation signatures of aggression and indolence in LDCT-detected lung cancers by comparing fast and slow-growing tumors identified as part of the ASCENT study.
36
From which study were patients recruited for the Epi-ASCENT project?
A) Epi-ASCENT study
B) SUMMIT study
C) ASCENT study
D) META study
B) SUMMIT study
37
Patients recruited for the Epi-ASCENT project were aged -.
55-77
38
True or False:
Patients recruited for the Epi-ASCENT project must currently be diagnosed with cancer.
False
39
What is the first aim of the Epi-ASCENT project?
A) To assess the effects of chemotherapy in treating lung cancer
B) To identify de novo tumor methylation signatures of aggression and indolence
C) To study the efficacy of radiation therapy in lung cancer patients
D) To analyze the molecular and cellular signatures of breast cancer
B) To identify de novo tumor methylation signatures of aggression and indolence
40
Epi-ASCENT aims to identify de novo tumor methylation signatures of aggression and indolence in LDCT-detected lung cancers by comparing fast to slow-growing tumor sub-groups identified in the ____ study.
Ascent
41
True or False:
One of the aims of Epi-ASCENT is to assess the methylation-based smoking and aging signatures of NSCLCs.
True
42
What is the second aim of the Epi-ASCENT project?
A) To identify de novo tumor methylation signatures of aggression and indolence
B) To analyze the effects of chemotherapy in treating lung cancer
C) To assess the methylation-based smoking and aging signatures of NSCLCs
D) To investigate the role of immune cells in lung cancer progression
C) To assess the methylation-based smoking and aging signatures of NSCLCs
43
Epi-ASCENT aims to assess the methylation-based smoking and aging signatures of NSCLCs, and test if these correlate with ____ rate.
Growth
44
True or False:
Epi-ASCENT aims to use integrated genomic analyses to combine epigenetic data, RNA-seq, and whole exome sequencing data to understand the role of genetics in tumor suppression and progression.
False
45
What is the third aim of the Epi-ASCENT project?
A) To assess the effects of chemotherapy in treating lung cancer
B) To identify de novo tumor methylation signatures of aggression and indolence
C) To use integrated genomic analyses to understand the role of epigenetics in tumor suppression and progression
D) To analyze the effects of radiation therapy in lung cancer patients
C) To use integrated genomic analyses to understand the role of epigenetics in tumor suppression and progression
46
True or False:
Epi-ASCENT aims to test if smoking and aging signatures correlate with growth rate in lung cancers.
True
47
Define Multi-omics Approach
his refers to performing analyses that combine more than one type of data (or ‘omics’), such as genetic sequencing (genomics), DNA methylation assessment (epigenomics), and measurement of gene expression levels of genes (transcriptomics).
48
What does the term "multi-omics approach" refer to?
A) Analyzing multiple diseases simultaneously
B) Using multiple data types in research analysis
C) Performing surgery on multiple patients at once
D) Combining multiple treatments in medical practice
B) Using multiple data types in research analysis
49
Multi-omics approach combines data from genetic sequencing (genomics), DNA methylation assessment (epigenomics), and measurement of gene expression levels of genes (____).
transcriptomics
50
True or False:
Multi-omics approach aims to analyze only one type of data at a time.
False
51
What is the purpose of combining DNAm with RNA-seq data?
A) To identify genetic variants associated with methylation sites
B) To test if growth-rate related DMP signatures correlate with differences in gene expression
C) To assess patient response to treatment
D) To analyze tumor morphology
B) To test if growth-rate related DMP signatures correlate with differences in gene expression
52
Combining DNAm with RNA-seq aims to test if growth-rate related DMP signatures correlate with differences in gene expression identified in ___.
RNA-seq
53
True or False:
The combination of DNAm with RNA-seq aims to analyze differences in tumor morphology.
False
54
What does WES stand for in this context?
A) Whole Exome Sequencing
B) Whole Epigenome Sequencing
C) Western Blotting and Electrophoresis
D) Whole Environmental Surveillance
A) Whole Exome Sequencing
55
Combining DNAm with WES aims to identify meQTLS, which stands for ___.
methylation quantitative trait loci
56
True or False:
Methylation sites associated with genetic variants are not identified through the combination of DNAm with WES.
False
57
hat is one potential patient impact of combining DNAm with other techniques, according to the provided information?
A) Development of invasive diagnostic methods
B) Improved understanding of tumor morphology
C) Development of non-invasive methods to predict tumor growth rate
D) Identification of non-specific therapy targets
C) Development of non-invasive methods to predict tumor growth rate
58
True or False:
Combining DNAm with other techniques does not contribute to the understanding of molecular causes of tumor aggression.
False
59
Potential Benefits of Taking Part in SUMMIT
Early detection: participation offers the potential of early detection of cancer, which can significantly improve treatment outcomes and survival rates.
Access to Advanced Screening Technologies: state-of-the-art screening technologies that may not be available outside of clinical trial settings.
Contributing to Medical Science: contribution to advancing scientific knowledge in developing diagnostic tools.
Monitoring and Follow-up: Regular monitoring and care may lead to early detection of other health issues (other than cancer).
Financial compensation: SUMMIT study provides £20 shopping voucher per follow-up.
60
What is one potential benefit of participating in clinical trials such as SUMMIT?
A) Increased risk of side effects
B) Access to advanced screening technologies
C) Uncertainty of risk
D) Limited access to individual results
B) Access to advanced screening technologies
61
Participating in SUMMIT offers the potential of early detection of cancer, which can significantly improve treatment outcomes and ___ rates.
Survival
62
True or False:
Participants in SUMMIT may contribute to advancing scientific knowledge in developing diagnostic tools.
True
63
Potential Disadvantages of Taking Part in SUMMIT:
ncertainty of Risk: Inherent risk of unknown side effects (from LCDT scans etc.).
Time and Commitment: Significant commitments involving multiple clinic visits and follow-up appointments.
Emotional Impact: fear and anxiety associated with cancer screening and diagnosis.
Limited Access to Individual Results: Participants may not receive individual test results depending on the stage of development.
64
What is one potential disadvantage of participating in clinical trials such as SUMMIT?
A) Financial compensation
B) Access to advanced screening technologies
C) Emotional impact associated with cancer screening and diagnosis
D) Contribution to advancing scientific knowledge
C) Emotional impact associated with cancer screening and diagnosis
65
Participants in SUMMIT may face uncertainty of risk due to the inherent risk of unknown side effects from ____ scans.
LDCT
66
True or False:
Participants in SUMMIT may have limited access to individual test results depending on the stage of development.
True
67
Define DNA Methylation
DNA methylation (DNAm) involves the addition of a methyl group (CH3) to cytosine residues in DNA.
68
What is DNA methylation?
A) Addition of a phosphate group to cytosine residues
B) Addition of a methyl group to cytosine residues
C) Removal of adenine residues from DNA
D) Addition of a hydroxyl group to thymine residues
B) Addition of a methyl group to cytosine residues
69
Majority of DNA methylation occurs at ___ sites.
CpG
70
True or False:
DNA methylation is not affected by genetics and lifestyle factors.
False
71
Tissue Biopsies (Method, pro, con)
Method: Extraction and analysis of sample cells/tissue.
Advantages: Gold standard for cancer profiling, easier to determine tumor-specific variants.
Limitations: Invasive, time-consuming, may not account for tumor heterogeneity.
72
Liquid Biopsies (Method, pro and cons)
Method: Sampling and analysis of biological fluids (blood, urine, saliva, etc.).
Advantages: Quick, easy to administer, minimally invasive, highly repeatable for regular screening.
Limitations: Higher likelihood of false negatives, not currently reproducible for all cancer types.
73
Which method involves the extraction and analysis of sample cells/tissue?
A) Tissue biopsies
B) Liquid biopsies
C) Nanopore sequencing
D) Bisulphite sequencing
A) Tissue biopsies
74
Liquid biopsies involve sampling and analysis of ___ fluids.
Biological
75
True or False:
Liquid biopsies are invasive and time-consuming.
False
76
Multiple Choice:
Which biomarker reflects genetic alterations?
A) CTCs
B) cfDNA
C) ctDNA
D) Exosomes
C) ctDNA
77
True or False:
microRNAs are specific to tumors and not influenced by other conditions.
False
78
What is a method used in methylation arrays?
A) PCR amplification
B) Bisulphite conversion of genomic DNA
C) Gel electrophoresis
D) Western blotting
B) Bisulphite conversion of genomic DNA
79
Methylation Arrays (Illumina 450k/EPIC) (method, pro and cons)
Method: Bisulphite conversion of genomic DNA, fluorescent staining, array scanning.
Pros: High sensitivity, time-effective, user-friendly, suitable for clinical samples.
Cons: Only detects previously determined regions, biased towards known CpG sites, affected by polymorphisms.
80
What is a method used in methylation arrays?
A) PCR amplification
B) Bisulphite conversion of genomic DNA
C) Gel electrophoresis
D) Western blotting
B) Bisulphite conversion of genomic DNA
81
True or False:
Methylation arrays are not suitable for clinical samples.
False
82
Nanopore Sequencing (method, pro and con)
Method: Direct detection of DNA through nanopore sensors.
Pros: Single nucleotide resolution, real-time analysis, reproducible.
Cons: Limited sequencing accuracy, context-dependent sequencing bias, higher cost.
83
What is a characteristic of nanopore sequencing?
A) Low sequencing accuracy
B) Indirect detection of DNA
C) Real-time analysis
D) Low cost
C) Real-time analysis
84
Nanopore sequencing allows direct reading of long nucleotide sequences and identification of modifications to the ___.
nucleotide
85
True or False:
Nanopore sequencing has limited sequencing accuracy.
True
86
Bisulphite Sequencing – Whole Genome (method, pro and con)
Method: Conversion of cytosine to uracil, methylation status determined through direct PCR sequencing.
Pros: Single-nucleotide resolution, whole genome coverage, high accuracy.
Cons: Requires lots of DNA, specialized bioinformatics tools, fresh cell/tissue samples.
87
What is a characteristic of bisulphite sequencing?
A) Low accuracy
B) Partial genome coverage
C) Conversion of uracil to cytosine
D) Single-nucleotide resolution
D) Single-nucleotide resolution
88
Bisulphite sequencing requires lots of ___.
DNA
89
True or False:
Bisulphite sequencing does not require specialized bioinformatics tools.
False
90
Which method involves the extraction and analysis of sample cells/tissue?
A) Tissue biopsies
B) Liquid biopsies
C) Nanopore sequencing
D) Bisulphite sequencing
A) Tissue biopsies
91
True or False:
Liquid biopsies are invasive and time-consuming.
False
92
Define SUMMIT:
SUMMIT is a large-scale clinical study aimed at individuals with significant smoking history, involving 25,000 Londoners aged 55-77. It is an observational cohort model initiated by UCL and UCLH, with the primary aims of clinically validating a blood test for early cancer detection and examining the feasibility of delivering low-dose CT screening for lung cancer.
93
Describe SUMMIT Participation Advantages:
Participation in SUMMIT offers several advantages, including the potential for earlier cancer diagnosis leading to increased survival rates, access to highly effective LDCT scans for early cancer detection, regular medical attention for monitoring cancer progress, access to new screening and treatments, free Lung Health Checks, smoking cessation referral, contribution to improving outcomes for future patients, and the opportunity to learn about scientific methods.
94
The possibility of false positives due to the high specificity of LDCT scans may lead to further ___ investigations or treatments.
invasive
95
What is a potential advantage of participating in the SUMMIT study?
A) Increased risk of false positives
B) Limited access to new screening and treatments
C) Regular medical attention for monitoring cancer progress
D) Decreased survival rates
C) Regular medical attention for monitoring cancer progress
96
Define ASCENT Trial:
The ASCENT trial is an extension of the SUMMIT study, focusing on individuals enrolled in SUMMIT or the NHS targeted lung check program, diagnosed with lung cancer, and referred for surgery. It aims to identify patterns indicating lung cancer for potential screening application and future understanding through genomic analysis of cancer cells.
97
Describe ASCENT Advantages and Disadvantages:
Advantages: Participation in ASCENT contributes to scientific knowledge, helps identify biomarkers, and may assist future patients.
Disadvantages: Patients won't directly benefit from participation, and individuals undergoing chemotherapy or radiotherapy prior to surgery cannot join the study.
98
What is a disadvantage of participating in the ASCENT trial?
A) Direct benefit to patients
B) Chemotherapy or radiotherapy prior to surgery allowed
C) Contribution to scientific knowledge
D) Identification of biomarkers
A) Direct benefit to patients
99
Define Precision Medicine:
Precision medicine is an approach for tailoring disease treatment and prevention to individual patient characteristics, such as genetics, environment, and lifestyle factors.
100
Precision medicine is an approach for tailoring disease treatment and prevention to individual ___ characteristics.
Patient
101
What does precision medicine aim to consider in tailoring healthcare?
A) Population averages
B) Disease statistics
C) Individual variability in genes, environment, and lifestyle
D) One-size-fits-all treatments
C) Individual variability in genes, environment, and lifestyle
102
Benefits of Precision Medicine for Patients and Society:
For Patients:
Personalized treatment plans tailored to individual characteristics, leading to improved efficacy.
Reduced adverse effects and complications due to targeted therapies.
Enhanced disease prevention and early detection through genetic risk assessment.
Improved patient outcomes and quality of life.
For Society:
More efficient use of healthcare resources by targeting treatments to those most likely to benefit.
Advancements in medical research and technology, driving innovation and economic growth.
Reduction in overall healthcare costs by avoiding ineffective treatments and hospitalizations.
Empowerment of patients through greater involvement in their healthcare decisions.
103
Define DNA Methylation:
DNA methylation is a process involving the addition of a methyl group to cytosine residues in DNA, which can influence gene expression and cellular function.
104
Describe Bhado-Singh et al Study:
Bhado-Singh et al utilized six artificial intelligence models to analyze DNA methylation patterns in CpG sites associated with lung cancer (LC). They identified specific differential methylation patterns in both coding and noncoding regions. Gene enrichment analyses revealed associations with various miRNAs, lncRNAs, and genes involved in critical lung cancer pathways such as KRAS, CDK4/6, MYC, PTEN, and MAPK1.
105
What did Heeke et al develop to differentiate the four SCLC subtypes?
A) Gene expression profiles
B) Protein markers
C) DNA methylation classifiers (DMC)
D) Tumor morphology analysis
C) DNA methylation classifiers (DMC)
106
Benefits of DNA Methylation Classifiers:
NA classifiers predicted drug responses and clinical outcomes in SCLC. For instance, SCLC-N cell lines were found to be more sensitive to the CDK inhibitor R-547, indicating potential treatment options tailored to specific SCLC subtypes.
107
How can DNA methylation analysis benefit patients?
A) Identifying patients with existing symptoms
B) Predicting response to therapies
C) Preventing disease occurrence
D) Providing immediate treatment options
B) Predicting response to therapies
108
Describe Benefits of DNA Methylation Analysis for Patients:
Earlier Detection: Helps identify patients at risk of certain diseases before symptoms appear, enabling earlier detection and intervention.
Improved Accuracy of Diagnosis: Tools like the Heidelberg brain tumor classifier utilize DNA methylation patterns to accurately diagnose tumor subtypes, distinguishing between aggressive and indolent tumors.
Avoidance of Unnecessary Interventions: Prevents unnecessary diagnostic testing and dangerous interventions, such as the removal of indolent tumors, which may cause more harm than the cancer itself.
Earlier Treatment of Aggressive Tumors: Facilitates early treatment of aggressive tumors, improving patient outcomes and survival rates.
Prediction of Treatment Response: DNA methylation-based assays can predict tumor response to different therapies, guiding healthcare decisions on the most effective treatment for individual patients. For instance, DNA methylation at the MGMT promoter predicts favorable response to alkylating agent treatments like temozolomide chemotherapy in glioblastoma tumors.
109
How does precision medicine reduce healthcare costs?
Precision medicine can lead to reduced healthcare costs by identifying the most suitable therapies for patients, thereby decreasing the need for further treatment. This optimization in treatment can save resources and money for healthcare systems.
110
What advancements has there been in precision medicine and what were its aim?
Projects like the 100,000 Genomes Project contribute to the advancement of medical knowledge by creating vast genomic healthcare data resources. This initiative aims to uncover answers for individuals with rare diseases or undiagnosed conditions, leading to increased diagnostic yield and facilitating quick identification through automated pipelines. Additionally, such projects often result in novel discoveries that can further enhance our understanding of diseases and treatment options.
111
How does precision medicine help with health equity?
Precision medicine considers individual differences in genetics, environment, and socioeconomic factors. By tailoring interventions to the specific needs of each individual, precision medicine has the potential to reduce disparities in healthcare access and outcomes across diverse populations, promoting health equity.
112
How can precision medicine benefit society?
a) Increased healthcare costs
b) Reduction in diagnostic yield
c) Advancement of medical knowledge
d) Ignoring individual differences
c) Advancement of medical knowledge
113
Precision medicine aims to reduce healthcare costs by identifying the most appropriate therapies for patients, thus _______________ the need for further treatment.
decreasing
114
True or False:
Precision medicine promotes health equity by considering individual differences in genetics, environment, and socioeconomic factors, thus reducing disparities in healthcare access and outcomes across diverse populations.
True
115
What is the NHS Genomics Strategy?
The NHS Genomics Strategy is a comprehensive plan developed by NHS England to integrate genomics into healthcare services over a five-year period. It aims to leverage genomic testing and precision treatments to improve patient outcomes and advance healthcare delivery.
116
How does the utilisation of AI help in the NHS Genomics Strategy?
Artificial Intelligence (AI) can play a crucial role in alleviating stress on the NHS by automating tasks and streamlining processes. For example, AI algorithms can assist in the analysis of medical imaging such as CT scans, reducing the burden on radiologists and increasing efficiency in diagnosis and treatment planning.
117
How can AI contribute to relieving pressure on the NHS?
a) Increasing the workload of radiologists
b) Automating tasks and streamlining processes
c) Decreasing efficiency in diagnosis
d) Adding stress to healthcare professionals
b) Automating tasks and streamlining processes
118
True or False:
The NHS Genomics Strategy includes steps to improve patient outcomes through genomic testing and precision treatments, but it does not address the integration of genomics into healthcare services.
False
119
Precision Medicine for Lung Cancer (LC):
Precision medicine for lung cancer involves tailoring treatment strategies based on the specific genetic alterations present in an individual's tumor cells. This approach aims to improve diagnosis, prognosis, and treatment outcomes by targeting molecular pathways involved in the development and progression of lung cancer.
120
What is AstraZeneca's precision medicine approach for lung cancer?
AstraZeneca's precision medicine approach for lung cancer focuses on identifying new biomarkers as therapeutic targets to enhance the diagnosis and treatment of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This approach aims to improve early detection and develop targeted therapies based on specific genetic mutations, such as mutations in the epidermal growth factor receptor (EGFR).
121
What is the LAURA Phase III trial?
The LAURA Phase III trial evaluated the efficacy of Tagrisso, a third-generation EGFR-tyrosine kinase inhibitor, in treating patients with Stage III EGFR-mutated NSCLC. Tagrisso works by blocking cell-signaling pathways that promote tumor cell growth. The trial involved administering 80mg once daily oral tablets of Tagrisso to patients after chemoradiotherapy.
Preliminary results from the trial have demonstrated statistically and clinically significant improvements in progression-free survival (PFS) compared to placebo. Additionally, overall survival data has shown a favorable trend for Tagrisso as a form of precision medicine for NSCLC.
122
Which company has focused recent research on defining new biomarkers as therapeutic targets to improve lung cancer diagnosis and treatment?
a) Pfizer
b) AstraZeneca
c) Merck
d) Johnson & Johnson
b) AstraZeneca
123
he LAURA Phase III trial evaluated the efficacy of ___________, a third-generation EGFR-tyrosine kinase inhibitor, in treating patients with Stage III EGFR-mutated NSCLC.
Tagrisso
124
True or False: Tagrisso is a first-generation EGFR-tyrosine kinase inhibitor used in the treatment of lung cancer.
False
125
What is population-wide cancer screening:
Population-wide cancer screening refers to systematic testing of individuals within a specific population to detect cancer at an early stage, often before symptoms develop. The goal is to reduce cancer-related morbidity and mortality by identifying tumors when they are more treatable.
126
What are the risks and benefits of population-wide cancer screening?
Cancer screening aims to detect tumors at an early stage, which can lead to more effective treatment and improved survival rates. However, there are risks associated with screening, such as false-positive results, overdiagnosis, and potential harm from subsequent diagnostic procedures or treatments. Despite these risks, population-wide cancer screening programs have been implemented for various types of cancer, including cervical, breast, colorectal, and lung cancer, with the aim of reducing cancer-related morbidity and mortality.
127
Which cancer screening method is commonly used for cervical cancer screening?
a) Mammography
b) FIT test
c) HPV primary testing
d) Flexible sigmoidoscopy
c) HPV primary testing
128
In the UK, the NHS invites individuals aged __________ to __________ years to send back a stool sample for a faecal immunochemical test (FIT).
50 to 74
129
True or False:
Lung cancer screening in the UK is primarily conducted using flexible sigmoidoscopy.
False
130
Which screening method is used for colorectal cancer screening that involves the direct visualization of the colorectum and the opportunity to biopsy?
a) gFOBT
b) FIT
c) Flexible sigmoidoscopy
d) Colonoscopy
c) Flexible sigmoidoscopy
131
True or False:
Stool-based tests for colorectal cancer screening include the detection of abnormal methylated regions of DNA associated with CRC.
True
132
What is the primary goal of cancer screening tests?
Answer Options:
a) To cure cancer
b) To detect cancer before symptoms appear
c) To treat cancer
d) To relieve cancer symptoms
b) To detect cancer before symptoms appear
133
True or False: Fast-growing or spreading cancers may not benefit significantly from early identification through screening.
True
134
What is the main objective of screening studies related to cancer?
Answer Options:
a) To identify the best treatment options for cancer
b) To test new cancer medications
c) To assess if mortality due to cancer decreases with screening
d) To measure cancer survival rates
c) To assess if mortality due to cancer decreases with screening
135
What is the financial impact of late-stage breast cancer diagnosis on the NHS?
Answer Options:
a) £100 million/year
b) £500 million/year
c) £700 million/year
d) £1 billion/year
c) £700 million/year
136
True or False: Catching cancer at earlier stages generally leads to an increase in healthcare costs.
False
137
What is the main objective of screening studies related to cancer?
Screening studies related to cancer aim to evaluate the effectiveness of screening programs in reducing mortality rates associated with the disease. These studies assess whether early detection through screening leads to improved outcomes and reduced cancer-related deaths.
138
What is the financial burden of late-stage cancer diagnosis on healthcare systems?
Late-stage cancer diagnosis imposes a significant financial burden on healthcare systems due to increased treatment costs and decreased effectiveness of interventions. For example, late-stage breast cancer diagnosis costs the NHS £700 million annually, highlighting the importance of early detection through screening programs.
139
Explain how catching cancer at earlier stages can impact healthcare costs.
Catching cancer at earlier stages through screening programs can lead to reduced healthcare costs. Early detection allows for less invasive and less costly treatment options, resulting in lower overall healthcare expenditure. Additionally, early-stage cancer treatment tends to be more effective and associated with better outcomes, further reducing long-term healthcare expenses.
140
What is the significance of sensitivity and specificity in cancer screening?
Sensitivity and specificity are measures used to evaluate the accuracy of cancer screening tests. Sensitivity refers to the test's ability to correctly identify individuals who have cancer (true positive rate), while specificity refers to its ability to correctly identify individuals who do not have cancer (true negative rate).
141
What are the risks associated with false negatives in cancer screening?
False negatives occur when screening tests show normal results despite the presence of cancer. This can lead to delays in treatment, resulting in a worse prognosis for patients as the disease progresses without intervention.
142
What is overdiagnosis, and how is it related to false positives in cancer screening?
Overdiagnosis occurs when screening tests incorrectly identify benign conditions or slow-growing cancers as harmful, leading to unnecessary treatment. False positives contribute to overdiagnosis by indicating cancer when it is not present, resulting in potentially harmful interventions.
143
What are the potential risks associated with repeated exposure to radiation in cancer screening?
Repeated exposure to radiation during screening procedures, such as CT scans, can increase the risk of developing cancer. Studies have shown that annual CT-related radiation exposure can lead to up to a 5.5% increase in the risk of lung cancer, highlighting the importance of minimizing unnecessary radiation exposure.
144
What are invasive procedures in cancer screening, and what are the associated risks?
Invasive procedures in cancer screening involve techniques such as sigmoidoscopy, colonoscopy, and aspiration biopsy. These procedures carry risks such as tears in the colon lining, pain, infection, and discomfort. Additionally, unclear results from mammograms may lead to unnecessary biopsies, increasing the risk of infection and discomfort for patients.
145
What is an observational study?
An observational study is a type of research where individuals are observed, or certain outcomes are measured, without any attempt to influence the outcome. Researchers merely observe and record data without intervening.
146
What are the types of observational studies?
Cross-sectional
Longitudinal
Ecological
Cohort
Case-control
147
What are the key characteristics of observational studies?
Observational studies typically involve passive observation by the investigator, with no control over the treatment or exposure variable. They focus on describing relationships or patterns without intervening to alter them.
148
What are the differences between observational and experimental studies?
Observational studies lack the level of intervention, randomization, and control over variables present in experimental studies. They also face ethical considerations differently and focus on establishing correlation rather than causality.
149
Differentiate between an observational and an experimental study using examples.
an observational study, researchers observe a random sample of adults and find that those who drink more coffee in the morning go to the bathroom more frequently.
In an experimental study, researchers randomly assign a group of adults to either drink two cups of coffee or none, then compare the bathroom breaks between the two groups.
150
What are the considerations for conducting a good observational study?
Conducting a good observational study involves careful study design to minimize bias and confounding factors. It also requires selecting participants wisely, employing appropriate data analysis techniques such as stratification and statistical adjustments, and conducting sensitivity analyses to assess hidden bias.
151
What type of observational study is Epi-ASCENT?
Epi-ASCENT is a cross-sectional study, where samples are collected at a singular point in time, and the prevalence of DNA methylation is assessed.
152
What are the key characteristics that make Epi-ASCENT an observational study?
No intervention from researchers
Analysis of associations
Exploratory and descriptive in nature
Population-based sampling
153
What is the significance of Epi-ASCENT's observational design?
Non-interference: Researchers do not intervene in the progression of the disease.
Natural course observation: Observing spontaneous changes in the tumor, including growth rates, genetic mutations, and interaction with surrounding tissues.
Potential for groundbreaking findings in tumor aggressiveness and treatment response.
154
What aspects of tumor aggressiveness can be identified through Epi-ASCENT?
Epi-ASCENT can identify specific characteristics predicting tumor aggressiveness, including growth speed, invasiveness, and metastatic potential.
155
How can Epi-ASCENT contribute to understanding treatment response?
Epi-ASCENT can reveal patterns of response to treatment, guiding future therapeutic strategies.
156
What future research directions can be informed by Epi-ASCENT?
Epi-ASCENT can generate hypotheses for future research, leading to experimental studies testing interventions impacting tumor behavior based on observational insights.
157
Prospective Studies: Pros
Higher Level of Evidence: Prospective studies provide a higher level of evidence compared to retrospective, case-control, and cross-sectional studies, enhancing the credibility of research findings.
Determining Causality: They enable the determination of the sequence of events, allowing researchers to hypothesize causality between variables.
Examining Multiple Outcomes: Prospective studies can examine the prevalence of multiple outcomes, offering a comprehensive understanding of the phenomena under investigation.
Cost-Effective: Compared to clinical trials, prospective studies are generally cheaper to conduct, making them a more cost-effective option for researchers.
Participant Safety: These studies do not expose participants to potential risk factors as they are merely observed over time, ensuring participant safety.
158
Prospective Studies: Cons
Lower Level of Evidence Than RCTs: Despite providing robust evidence, prospective studies still hold a lower level of evidence compared to randomized controlled trials (RCTs), limiting their reliability in certain contexts.
Risk of Withdrawals and Loss to Follow-Up: There is a chance of participant withdrawals and loss to follow-up over the course of the study, potentially affecting the validity of the results.
Large Sample Size Requirement: Prospective studies often require large sample sizes to detect meaningful associations, which can be challenging to recruit and maintain.
Longer Duration: These studies typically require a longer duration to observe outcomes, leading to increased time and resource investment.
Prone to Bias: Prospective studies are prone to selection and confounding bias, which may influence the accuracy of the findings.
Higher Cost: While generally less expensive than clinical trials, prospective studies are still more costly to conduct compared to retrospective and cross-sectional studies, posing financial challenges for researchers.
159
Define DNAm Patterns
Patterns in DNA methylation (DNAm) refer to the arrangement of methyl groups on the DNA molecule, which can vary across different genomic regions and cell types.
160
Describe Hypomethylation of Promoter Regions
Hypomethylation of promoter regions involves reduced methylation levels, leading to increased gene expression. This phenomenon is associated with cell proliferation, migration, and tumour progression.
161
Describe Hypermethylation of Promoter Regions
Hypermethylation of promoter regions involves increased methylation levels, resulting in gene silencing. This process can lead to the inactivation of tumour suppressor genes and promote tumour growth.
162
What is the consequence of hypomethylation of genes involved in angiogenesis?
a) Inhibition of cell proliferation
b) Promotion of tumour growth
c) Induction of apoptosis
d) Inactivation of oncogenes
b) Promotion of tumour growth
163
What is the primary tumour methylation pattern associated with?
a) Increased patient age
b) Improved patient prognosis
c) Patient's ethnic background
d) Patient's dietary habits
b) Improved patient prognosis
164
Describe the Relationship Between DNAm Patterns and Patient Outcome
DNAm patterns can serve as robust biomarkers for predicting patient outcome, including recurrence-free survival and long-term survival rates.
165
Define Multidrug Resistance (MDR)
Multidrug resistance (MDR) refers to the ability of cancer cells to resist the effects of multiple chemotherapeutic drugs, leading to treatment failure and disease progression.
166
What is a potential therapeutic strategy for reversing hypermethylation-induced drug resistance?
a) Administration of DNMT inhibitors
b) Hypomethylation of key genes
c) Activation of tumour suppressor genes
d) Promotion of angiogenesis
a) Administration of DNMT inhibitors
167
Describe the Consequences of DNAm Patterns on Apoptotic Pathways
Changes in DNAm patterns can affect apoptotic pathways, influencing the susceptibility of cancer cells to undergo programmed cell death in response to therapy or environmental cues.
168
Describe the Impact of Exercise on DNAm Patterns
Exercise-induced changes in DNAm patterns, particularly among older individuals, suggest that physical activity may play a role in reducing cancer risk by modulating epigenetic modifications.
169
What is a potential outcome of hypermethylation of genes involved in DNA repair?
a) Genomic instability
b) Enhanced tumour suppression
c) Reduced angiogenesis
d) Increased cell proliferation
a) Genomic instability
170
Describe the Role of Hypermethylation in Therapy Resistance
Hypermethylation-induced gene silencing can contribute to therapy resistance by downregulating tumour suppressor genes and promoting multidrug resistance in cancer cells.
171
Describe the Role of Hypomethylation in Therapy Resistance
Hypomethylation of gene promoters can lead to drug resistance by upregulating genes involved in multidrug resistance, cell proliferation, and inhibition of apoptosis, thereby promoting tumour survival.
172
Hypermethylation typically leads to _______ gene expression or gene silencing.
Decreased
173
Describe the Impact of DNAm Patterns on Metastasis
Changes in DNAm patterns can affect genes involved in cell adhesion and invasion, promoting metastasis, which contributes to tumour aggressiveness and lethality.
174
Describe Liquid Biopsy
Liquid biopsy is a minimally invasive approach for detecting cancer early by analyzing various biomarkers, such as cell-free DNA, circulating tumour cells, and exosomes, present in bodily fluids like blood, urine, saliva, and sputum.
175
Which of the following is an advantage of liquid biopsy?
a) Invasive procedure
b) Limited to detecting primary tumours
c) Detects tumour recurrence
d) Low sensitivity
c) Detects tumour recurrence
176
Define Enzyme-linked Immunosorbent Assay (ELISA)
ELISA is a competitive assay used to quantify methylated cytidine in DNA samples. It is rapid, sensitive, and cost-effective but may suffer from cross-reactivity and low specificity.
177
Describe Luminometric Methylation Assay (LUMA)
LUMA is a DNA methylation analysis method based on DNA digestion using specific enzymes. It offers high sensitivity and cost-effectiveness but can only detect differences in methylation within CpG sites.
178
What is a disadvantage of LUMA?
a) High specificity
b) Low sensitivity
c) Requires large DNA input
d) Cannot detect differences in methylation within CpG sites
d) Cannot detect differences in methylation within CpG sites
179
Describe Whole-genome Bisulfite Sequencing (WGBS)
WGBS is a next-generation sequencing method that analyzes each CpG site of bisulfite-converted DNA. It offers high accuracy, sensitivity, and repeatability but can be expensive and complex to operate.
180
What is an advantage of WGBS?
a) Low accuracy
b) Limited repeatability
c) Insensitive
d) Requires minimal DNA input
d) Requires minimal DNA input
181
Describe Human Methylation 850K BeadChip
The Human Methylation 850K BeadChip is a DNA methylation analysis tool based on probe hybridization, capable of analyzing over 850,000 CpG sites. It offers sensitivity, time-effectiveness, and user-friendliness.
182
What is a disadvantage of the Human Methylation 850K BeadChip?
a) Detects all DNA methylation sites
b) Limited sensitivity
c) Expensive
d) Requires extensive DNA input
c) Expensive
183
Describe Global DNA Methylation Analysis
Global DNA methylation analysis involves quantifying the overall methylation status of DNA samples using methods like ELISA or LUMA. It provides insights into the global methylation patterns of genomic DNA.
184
Describe Whole-genome DNA Methylation Analysis
Whole-genome DNA methylation analysis methods, such as WGBS and BeadChip assays, examine methylation patterns across the entire genome, offering comprehensive insights into DNA methylation dynamics.
185
Which method is suitable for analyzing each CpG site of bisulfite-converted DNA?
a) ELISA
b) LUMA
c) WGBS
d) BeadChip
c) WGBS
186
Describe the Advantages of DNA Methylation Analysis
DNA methylation analysis provides valuable information about epigenetic modifications associated with cancer progression, drug resistance, and patient outcomes, aiding in personalized treatment strategies
187
What is a potential consequence of hypomethylation in cancer cells?
a) Decreased gene expression
b) Increased drug sensitivity
c) Enhanced tumour growth
d) Improved prognosis
c) Enhanced tumour growth
188
Define Multi-omics
Multi-omics refers to the simultaneous analysis of multiple omics data types, such as genomics, transcriptomics, and epigenomics, to gain a comprehensive understanding of biological systems.
189
Describe the Need for a Multi-omic Approach
The progression of lung squamous cell carcinoma (LUSC) from mild dysplasia to cancer poses challenges in diagnosis and treatment. Autofluorescence bronchoscopy (AFB) lacks the ability to differentiate lesions that progress to cancer from those that regress, leading to unnecessary surgeries. Hence, a multi-omic approach is necessary to identify molecular signatures associated with tumour aggression and guide non-invasive treatments.
190
Which technique is commonly used to study early tumorigenesis in humans but has limitations in distinguishing lesions that progress to cancer?
a) Immunohistochemistry
b) Autofluorescence bronchoscopy (AFB)
c) Positron emission tomography (PET) scan
d) Magnetic resonance imaging (MRI)
d) Magnetic resonance imaging (MRI)
191
Describe the Benefits of a Multi-omic Approach
A multi-omic approach helps identify molecular alterations driving tumour aggression, including mutations, altered gene expression, and DNA methylation changes. This comprehensive analysis can unveil potential therapeutic targets and enable non-invasive treatments for less aggressive tumours.
192
Describe the Study Conducted by Teixeira et al. (2019)
Teixeira et al. (2019) conducted a study involving 140 participants with carcinoma in situ (CIS) who underwent autofluorescence bronchoscopy (AFB) and biopsies every 4 months. Molecular analysis of DNA, RNA, and epigenetic profiles was performed on CIS lesions that either progressed to cancer or regressed. The study aimed to identify molecular differences associated with tumour progression.
193
Which gene showed both hypermethylation and underexpression in progressive CIS samples compared to regressive ones?
a) TP53
b) NKX2-1
c) EGFR
d) KRAS
b) NKX2-1
194
Define Chromosomal Instability (CIN) Genes
Chromosomal instability (CIN) genes are a group of genes associated with alterations in chromosomal structure and number, which can contribute to tumour development and progression.
195
Describe the Role of CIN Genes in CIS Lesions
In Teixeira et al.'s study, five genes associated with chromosomal instability (CIN) showed both altered expression and methylation patterns in CIS lesions. These genes were upregulated and exhibited altered methylation, potentially contributing to tumour progression.
196
What was a significant finding regarding mutation rates in CIS lesions that regressed compared to those that progressed?
a) Higher mutation rates in regressive lesions
b) Lower mutation rates in regressive lesions
c) Similar mutation rates in regressive and progressive lesions
d) Absence of mutations in regressive lesions
b) Lower mutation rates in regressive lesions
197
Describe the Importance of Clinical Trials in Utilizing Study Data
Despite promising findings in Teixeira et al.'s study, clinical trials are essential to validate the effectiveness of potential therapies identified through multi-omic analyses before their clinical application.
198
Describe the Role of DNA Methylation Analysis in Multi-omics
DNA methylation analysis is a crucial component of multi-omics studies, providing insights into epigenetic modifications associated with tumour progression. Techniques such as whole-genome bisulfite sequencing and methylation-specific PCR are commonly used for this purpose.
199
Define Mutation Rates
Mutation rates refer to the frequency at which changes occur in the DNA sequence of a gene or genome within a population over a specified period.
200
What is the primary aim of performing multi-omics analysis in cancer research?
a) To identify novel therapeutic targets
b) To improve diagnostic accuracy
c) To reduce treatment costs
d) To study disease epidemiology
a) To identify novel therapeutic targets
201
Describe the Molecular Significance of Altered Expression and Methylation Patterns in CIN Genes
Altered expression and methylation patterns in chromosomal instability (CIN) genes suggest their involvement in tumour progression. Upregulation of these genes, coupled with aberrant methylation, may contribute to genomic instability and malignant transformation.
202
Define Autofluorescence Bronchoscopy (AFB)
Autofluorescence bronchoscopy (AFB) is a diagnostic technique that uses fluorescence imaging to detect early signs of lung cancer by visualizing changes in the bronchial mucosa under ultraviolet light.
203
Define: Early Diagnosis of Cancer
Early diagnosis of cancer refers to identifying cancer at its initial stages, often before symptoms become apparent, allowing for prompt intervention and treatment.
204
Describe: Impact of Early Diagnosis
Early diagnosis of cancer leads to increased treatment options, improved long-term survival rates, and enhanced quality of life for patients.
205
What percentage of lung cancer patients survive for 5 years or more if diagnosed at the earliest stage?
A) 4 in 10
B) 6 in 10
C) 8 in 10
D) 9 in 10
B) 6 in 10
206
Define: Targeted Lung Health Checks (TLHC)
Targeted Lung Health Checks (TLHC) are programs designed to offer lung health assessments, including low-dose CT scans, to individuals at high risk of developing lung cancer, such as current or former smokers.
207
Multiple Choice: Approximately how many cancers have been diagnosed through Targeted Lung Health Checks (TLHC)?
A) 500
B) 1000
C) 1500
D) 2000
C) 1500
208
Describe: Impact of Targeted Lung Health Checks (TLHC)
LHC has led to the diagnosis of over 1500 cancers, with approximately 76% detected at stage 1 or 2, resulting in earlier treatment and improved outcomes for patients.
209
True or False: TLHC programs are established in all regions of the UK.
False
210
Define: Low-dose CT Scan
low-dose CT scan is a medical imaging technique that uses X-rays to create detailed images of the lungs while minimizing radiation exposure, making it suitable for early cancer detection screenings.
211
Which of the following is a common phenotype of cancer related to DNA methylation alterations?
A) Hypermethylation
B) Hypomethylation
C) Mutation
D) Both A and B
D) Both A and B
212
Describe: Hypermethylation's Role in Cancer Development
Hypermethylation of CpG island promoters in cancer cells leads to decreased gene expression, particularly of tumor suppressor genes, DNA repair genes, and cell cycle regulators, promoting abnormal cell growth and cancer development.
213
True or False: Hypermethylation typically results in increased gene expression.
False
214
Define: CpG Methylation
CpG methylation refers to the methylation of cytosine nucleotides followed by guanine nucleotides in the DNA sequence, often found in CpG islands near gene promoter regions.
215
Which gene mutation can lead to inactivation of DNA repair mechanisms and subsequent genomic instability?
A) MGMT
B) MLH1
C) P53
D) IRAK3
B) MLH1
216
Describe: Hypomethylation's Role in Tumour Development
Hypomethylation, while less frequent than hypermethylation, can activate oncogenes and proto-oncogenes by increasing accessibility to promoter regions. This upregulation of oncogenes contributes to abnormal cell growth and tumour development.
217
True or False: Hypomethylation is a common event in late-stage tumour development.
False
218
Which gene is commonly hypermethylated in cancer, leading to decreased DNA repair capacity?
A) MGMT
B) MLH1
C) IRAK3
D) P53
A) MGMT
219
True or False: Hypermethylation can contribute to mutational hotspots, such as inactivating C to T transitions at the p53 tumour suppressor gene.
True
220
Describe: Impact of DNA Methylation on Imprinted Locus 1GF2/H19
Hypermethylation of the imprinted locus 1GF2/H19 can result in loss of imprinting, leading to increased expression of IGF2, a growth factor associated with tumour development.
221
Describe: Potential Clinical Implications of Hypermethylation
nderstanding hypermethylated genes in cancer, such as MGMT, MLH1, IRAK3, and P53, can aid in developing targeted therapies and diagnostic biomarkers for early detection and treatment monitoring.
222
Precision medicine aims to:
A) Standardize treatments for all patients
B) Tailor treatments to individual patient characteristics
C) Focus solely on genetics
D) Increase adverse events
B) Tailor treatments to individual patient characteristics
223
Which of the following is an example of reduced adverse events with precision medicine?
A) Increased frequency of adverse reactions
B) Higher hospitalization rates
C) Decreased frequency of adverse reactions
D) Unchanged safety concerns
C) Decreased frequency of adverse reactions
