Cancer Genetics Flashcards
(45 cards)
1
Q
classes of genetic damage in cancer
A
- proto-onco genes
- tumor suppressor genes
- apoptosis
- DNA repair
2
Q
driver mutation
A
- cause of malignant phenotype
- genes that are in congrol
3
Q
initiating mutation
A
the first driver mutation/ first cell that is mutated
4
Q
passenger mutation
A
- no phenotypic consequences
- genes don’t do that much/ not in control
5
Q
major phases of cancer evolution
A
- breakthrough phase
- expansion phase
- invasive phase
6
Q
what is the breakthrough phase?
A
- one bad cell/ driver cell causes mutation
- divides abnormally
7
Q
what is the expansion phase?
A
- still benign
- proliferation of cells locally
8
Q
what is the invasive phase?
A
- more driver gene mutations
- tumor invades distant organs
9
Q
oncogene
A
mutation in a single allele is tumorigenic
10
Q
tumor suppressor gene
A
- mutation required in both alleles
11
Q
first hit germ-line
A
- inheritance of a single germ-line mutation increases a chance of receiving a second somatic hit causing cancer
12
Q
second hit somatic-line
A
- happens in sporadic forms of disease by two sequential somatic mutations
13
Q
retinoblastoma
A
- rare type of eye cancer of early childhood that develops in retina
- caused by RB1
14
Q
sporadic Rb
A
- both alleles of RB1 are mutated
- two hits after birth
15
Q
inherited Rb
A
- first hit mutation is inherited
- second hit is in somatic line after birth
- have multiple tumors and at an earlier age
16
Q
loss of heterozygosity
A
- change from heterozygous state to homozygote state in the tumor DNA
- have mutated allele, normal functioning allele is deleted in second hit
- hallmark for tumor suppressor genes
17
Q
ulcerative colitis
A
- chronic inflammation causing ulcers in the inner lining of large intestine
- chronic inflammation makes colon more susceptible to ROS
- inflammation -> dysplasia -> carcinoma
- associated with p53 gene
18
Q
what is the p53 gene
A
tumor-suppressor gene
19
Q
SNPs and cancer
A
- most common inherited mutation
- GWAS used to compare SNP of diseased vs control to identify cancer genes
- can be used to identify risk factors associated with cancer in certain populations
20
Q
cancers caused by obesity
A
- meningioma
- thyroid cancer
- adenocarinoma
- esophageal cancer
- post-menopausal breast cancer
- liver cancer
- gallbladder cancer
- stomach cancer
- pancreatic cancer
- kidney cancer
- colorectal cancer
- prostate cancer
- ovarian cancer
- multiple myeloma
- endometrial cancer
21
Q
obesity and cancer links
A
- obesity is a chronic state of inflammation
- IGF-1 stimulates cell growth
- leptin released, promotes cell proliferation
- adiponectin not released, prevents cell growth
- fat tissue produces estrogen
- gut microbes activate bacteria to secrete chemicals that damage DNA
22
Q
major pathways affected in obesity and cancer
A
- mTOR
- AMP-APK
- both involved in cell growth and metabolism
- mTOR more strongly associated with GI cancers
23
Q
how do viruses cause cancer?
A
- viral oncogene expression
- genome integrations
- chronic activation of inflammatory response
24
Q
connection between chronic inflammation and cancer
A
- increased ROS causes DNA damage
- anti-apoptotic genes activated
- angiogenesis with chronic inflammation
25
lifestyles of oncoviruses
- all parts of viral genome expressed, viral replication, cell lysis and death
- viral DNA integrated, transformation of cells
26
HPV
- can cause genital warts
- cancers: penile, uterine, cervical, anal, oral, laryngeal
- have early genes and late genes expressed on virus
27
HPV lifecycle
- virus infects basal layer of epithelium
- early genes stimulate growth and replication of viral DNA
- late genes cause virus to assemble to top of epithelium
28
Epstein Bar virus
- type of herpes virus
- infects oral cavity
- affects B cells and results in a lot of blast B cells and memory B cells
- latency- EBV shuts down protein-encoding genes
- if resting B cell reactivated causes virus to proliferate
29
HBV and HCV
- hepatitis B and C
- associated with hepatic carcinoma (HCV more so)
- infection -> hepatitis -> cirrhosis -> hepatic carcinoma
- have inflammation, ROS, cellular growth signals, no apoptosis
30
why is HBV different?
- has covalently closed circular DNA - cccDNA
| - cccDNA causes therapy to fail, is a template for transcription and translation of the virus
31
RNA oncoviruses
- aka retrovirus
- instead of having DNA converting to RNA, start with RNA use reverse transcriptase to make dsDNA
- dsDNA integrated into host cell
- RNA copied from integraded DNA and spliced to give mRNA
32
HTLV-1
- human T cell leukemia virus 1
- causes adult ATLL
- have tax protein
33
what is the function of tax proteins
- regulatory protein
- if there is DNA damage it disables DNA repair system and cell cycle checkpoints
- gives virus advantage to survive and proliferate
- retrovirus
34
what bacteria associated with cancer?
- H. pylori
| - can cause gastric cancer
35
H. pylori infection
- causes inflammation -> DNA damage and changes in cell proliferation
- somatic mutations due to errors in replication or DNA repair
- epigenetic changes
36
cancer stem cells
- cell within a tumor that can self-renew and cause heterogenous lineage of cancer cells
37
what is the cancer stem cell hypothesis?
- malignancies originate from small populations of stem cells
- can initiate characteristics of cancer cells
38
origins of cancer stem cell hypothesis
- CSC arise from mutated stem cell so can self renew
- CSC arise from progenitor cells with partial self renewal
- CSC arise from differentiated cells which de-differentiate to become more stem-cell like
39
metastatic stem cells (metSC)
- any disseminated tumor cell capable of initiating clinically detectable tumor distant from primary tumor
40
why are metSC important?
- can be found in distant organs
- survive after cancer treatment
- causes uncontrollable metastasis
41
CSC targeted cancer therapy
- traditional treatments dont kill CSC, kills tumor cells -> tumor shrinks but can come back
- CSC therapy kills CSC, tumor cannot proliferate and it will shrink
42
Alzheimer's disease
- irreversible, progressive brain disease
- characterized by amyloid plaques and tau tangles
- causes death of nerve cells
- either early or late onset
43
amyloid precursor proteins (APP)
- normally APP gets cleaved in different sections
| - mutation in APP -> abnormal cleavage -> plaques aggregate -> neuron miscommunication
44
early onset AD genetic links
- chromosomes 1, 14, 21
| - mutations in PS1, PS2, and APP
45
late onset AD genetic links
- chromosomes 14 and 19
| - mutation in APOE4
