Test 2 Slide Decks Flashcards

Question

How many new cases of cancer are reported each year? What is the leading cause of death in the US?

Answer 1

Around 1.6 million new cases of cancer are reported per year in the United States. Cancer is the second leading cause of death in the United States (heart disease being the first) in recent years with the exception of years heavily impacted by the COVID-19 pandemic.

Answer 2

True. Cancer affects people of all ages, though it is higher in older individuals

Answer 3

Often an accumulation of multiple mutations in the genome is what causes a normal cell to become a cancerous cell With age, mutations accumulate in the genomes of our cells. This is why cancer increases with age

Answer 4

The mutations can make a cell have an altered phenotype and might have a disruption in its natural growth/death pathways. These cells replicate and divide like every other cell in the body, thus accumulating mutant cells and forming a tumor

Answer 5

The cell cycle is the specific set of events leading to the development of two daughter cells (replication)

Answer 6

Major phases of the cell cycle: * Interphase: DNA is replicated * Mitotic phase: DNA and contents of cytoplasm are separated into 2 cells

Answer 7

division of cell nucleus

Answer 8

separation of cytoplasm

Answer 9

Checkpoints exist in the cell cycle to monitor DNA for mistakes. DNA replication is an inaccurate process - Occasionally the enzyme responsible for DNA replication inserts a wrong nucleotide base (e.g. an A instead of a G) - This might sound like a bad thing on first glance, but this helps organism’s ability to evolve (each cell produced may not be exactly the same as parent) DNA polymerase enzyme should match bases correctly (G with C, A with T) but sometimes mistakes are made

Answer 10

G1 checkpoint: check for genomic DNA damage G2 checkpoint: check for cell size and that all chromosomes have been replicated M checkpoint: makes sure the pair of chromosomes are attached to spindle

Answer 11

Normal positive cell cycle regulator genes (promote cell division) that if mutated can cause the cell to become cancerous (e.g. push past checkpoints during division)

Answer 12

Normal negative cell cycle regulator genes (prevent uncontrolled cell division) that if mutated can cause the cell to become cancerous (e.g. can’t stop dividing, p53)

Answer 13

p53 monitors DNA for damage and signals apoptosis if damage is detected If p53 is mutated, there is no evaluation of DNA damage and there is a progression toward tumor development

Answer 14

Some biomarker tests can find genetic changes that you may have been born with (inherited) that increase your risk of cancer or other diseases. These genetic changes are also called germline mutation.

Answer 15

Inherited gene mutations play a role in about 10% of all cancers There are around 50 known hereditary forms of cancer

Answer 16

Inherited mutations in the BRCA1 and BRCA2 genes are associated with hereditary breast and ovarian cancer syndrome These mutations are associated with an increased lifetime risk of breast and ovarian cancers in women. Several other cancers have been associated with this syndrome, including pancreatic and prostate cancers, as well as male breast cancer.

Answer 17

Testing for hereditary mutations in patients with breast cancer has evolved significantly since the 1990s. Initial testing involved BRCA1 and BRAC2 sequencing and evolved to include larger deletions and duplications in BRCA1 and BRAC2. Next-generation sequencing allows timely testing of multiple genes, many of which have differing estimated risks for breast and other cancers. With the expansion of genes evaluated, as well as the need for more comprehensive understanding of clinical management, multiple guidelines for testing have been developed. This expansion has come with significant controversies, most notably who to test and which genes should be included

Answer 18

There are also more targeted treatments available for specific types of cancers with known mutations.

Answer 19

The need for hereditary cancer testing for all patients diagnosed with advanced breast cancer. * Tumor genomic profiling is the standard of care for many types of malignancies and is becoming increasingly important in the management of advanced breast cancer. * Today, molecular testing is now part of the clinical management for the majority of patients with breast cancer.

Answer 20

The presence of inherited, or de novo, mutations * Tumor DNA testing is different from genetic testing that is used to find out only if someone has inherited mutations that make them more likely to get cancer. Inherited mutations are those you are born with. They are passed on to you by your parents. * Again, this type of testing is also often linked to specific treatments for those specific de novo mutations * These tests may also involve genomic level analyses and look at the number of genetic changes in your cancer (what’s known as tumor mutational burden). This information can help figure out if a type of immunotherapy known as immune checkpoint inhibitors may work for you.

Answer 21

Precision medicine (a.k.a. personalized medicine) is an approach to medical care in which disease prevention, diagnosis, and treatment are tailored to the genes, proteins, and other substances in your body. * For cancer treatment, precision medicine means using biomarker and other tests to select treatments that are most likely to help you * Despite much progress in this area, the precision medicine approach to cancer treatment is not yet available to all patients.

Answer 22

With the increased emphasis on patient-driven health care and readily available access to patients as consumers through the internet and media, many genetic testing companies are marketing directly to consumers. * Companies offer genetic testing for nonmedical information, including ethnicity, athletic performance, behavior, aging, metabolism, or other traits. * Also included may be testing for medically significant conditions, including carrier status for genetic diseases such as cystic fibrosis, hemochromatosis, and variations that increase the risk of breast, ovarian, and other cancers.

Answer 23

a kind of breast cancer that does not have any of the receptors that are commonly found in breast cancer. Triple-negative breast cancers are defined as tumors that lack expression of estrogen receptor (ER), progesterone receptor (PR), and HER2

Answer 24

black and hispanic women

Answer 25

a HER2- specific antibody which binds to the cancer cells and disrupts the uncontrolled growth cycle

Answer 26

The HER2 gene is present in all human cells and it is responsible for the division and growth of the cell. * But too many HER2 genes in a cell can result in an over- abundance of receptors on the cell’s surface; this is called protein over-expression. * Over-expression causes cells to divide uncontrollably which leads to the spread of cancer

Answer 27

Multiple studies have indicated that triple-negative breast cancers, as a group, are associated with an adverse prognosis. * HER2-positive breast cancers were also associated with a poor prognosis until targeted antibody therapy with trastuzumab came into use. No such biologic therapy is available for triple-negative or basal-like breast cancer * Triple-negative breast cancer is typically treated with a combination of surgery, radiation therapy, and chemotherapy. * Heterogeneity is also seen in how they respond to treatment which likely reflects the fact that TBNC is itself a diverse group of cancers

Answer 28

Phenotype is described as the observable properties (i.e., traits) of an organism that result from a combination of genotype and environment * Phenotype is therefore influenced by a combination of their inherited genes and environmental effects

Answer 29

the range of phenotypes that can be seen in a given trait across a population * A simple way of thinking of phenotypic variation is that it can be explained by genotypic variation, but the truth is that it is also impacted by environmental variation (and similarly there is a huge range here in the extent to which genes vs environment impact a given trait) Examples: * Sickle cell disease: being more deterministic from a genetic level (if HbSS, you have SCD) * Malaria (complex disease): being a combination of genetic and environmental (if HbAA and in an area with high mosquito exposure and endemic malaria, the more likely you are to have the disease. But having HbAA on its own doesn’t mean you will get malaria)

Answer 30

Some element of randomness is also at play * Random effects also add variation as they impact the phenotype. * Populations living in a habitat may all experience the consistent environmental effects, but each individual may still have random chance variation during their lives. * For example, all members of the society live in a malaria-endemic area, but a particular family lives right next to a pond with high mosquito-breeding behavior. Here, malaria-endemnicity is the consistent environmental effect and the chance of being near a mosquito breeding site is a “random” effect.

Answer 31

VP = VG + VE + e * This concept can be thought of in terms of an equation. * The total variation in phenotype (VP) is equal to the variation in phenotype from the inherited genetic factors (VG) plus the variation in phenotype coming from the non-inherited environmental factors (VE) plus random error e

Answer 32

Genotype-Environment interaction means that not all genotypes have the same reaction to the environmental stressor, and/or not all environmental effects have the same reaction in all genotypes

Answer 33

For GWAS to work, we need A LOT of individuals in both the control and affected populations. This is mainly to account for environmental effects. * If the effects of the environment are really strong for a given trait (often we think this is the case for cancer, heart disease) then we need to design our study to control for all these effects. Typically, cancer studies have very large N * Some studies restrict population to certain age groups and health statuses

Answer 34

They: 1. Obtain a better estimate of the population-attributable risk for genetic and environmental risk factors by accounting for their joint interactions. 2. Strengthen the associations between environmental factors and diseases by examining these factors in genetically susceptible individuals. 3. Help to dissect disease mechanisms in humans by using information on susceptibility (and resistance) genes to focus on the biological pathways that are most relevant to that disease, and the environmental factors that are most relevant to the pathways. 4. Determine which specific compounds in the complex mixtures of compounds that humans are exposed to (such as diet or air pollution) cause disease. 5. Use the information on biological pathways to design new preventive and therapeutic strategies. 6. Offer tailored preventive advice that is based on the knowledge that an individual carries susceptibility or resistance alleles.

Answer 35

An international effort that started in 1991 and concluded in 2003 with the first complete human genome sequence that was made available to scientists for study 3 billion bases were sequence, covering 99% of the human genome’s gene-containing regions, and revealing that we have just over 20,000 genes The identification of over 3 million SNPs, indicating diversity in the human genome

Answer 36

It doesn’t show after all what happens TO the DNA. It just shows what is available to be expressed by that organism (like a library of songs but which one is being played, at what time and how much?)

Answer 37

It can affect us directly in real time in a temporary way (e.g. the UV light from the sun can cause a sun burn in the skin cells). So the phenotype of sunburn results from a combination of genome (e.g. genes for melanin) and environment (UV exposure amount).

Answer 38

Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes. Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Epigenetic modifications can manifest as commonly as the manner in which cells terminally differentiate to end up as skin cells, liver cells, brain cells, etc.

Answer 39

1. DNA methylation 2. histone modification 3. non-coding RNA (ncRNA)-associated gene silencing are currently considered to initiate and sustain epigenetic change.

Answer 40

Involves the addition of a methyl group to the DNA. The methyl group gets added to specific places on the DNA, where it blocks the ability of a polymerase to attach to DNA and“read” the gene. This process is reversible. A methyl group can be removed through what is called demethylation. Methylation is primarily a way to turn genes “off” , whereas demethylation turns genes “on.”

Answer 41

The DNA double helix is not just floating around loosely in the nucleus. It is wrapped around proteins called histones. When histones are tightly packed together, the polymerase cannot access the DNA as easily, so the gene is turned “off.” When histones are loosely packed, more of the DNA is exposed and can be accessed by the polymerase, so the gene is turned “on.” Methyl groups can be added or removed from histones to make the histones more tightly or loosely packed, turning genes “off” or “on.”

Answer 42

Non-coding RNA helps control gene expression through binding and altering coding RNA. Non-coding RNA can also recruit proteins that modify histones, which can in turn, turn genes “on” or “off.”

Answer 43

DNA methyltransferases (DNMTs)

Test 2 Slide Decks Flashcards

(70 cards)