FINALS LEC 1: CANCER GENETICS AND GENOMICS Flashcards by Sunwoo's Berry

type of disease in which certain cells become able to DIVIDE MORE OFTEN, leading to an abnormal growth (a tumor) or disruption of a proportion of blood cell types (a “liquid” tumor).
may be inherited or due to environmental factors such as UV radiation or toxic

CANCER

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One researcher calls the accumulating DNA changes that lie behind cancer is what we called?

GENOMIC SCARS

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WHOLE-BODY LEVEL
DIAGNOSIS:
SYMPTOM TESTS

TEST TO UNDERGO:

BIOMARKERS
IMAGING
MUTATION DETECTION

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CELLULAR LEVEL
-skin cancer cells divide faster than surrounding cells

DISRUPTED PATHWAYS:

CELL FATE
CELL SURVIVAL
GENOME MAINTENANCE

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study of how our behaviors or environmental factors make cause changes that can affect our genes
- REVERSIBLE
- does not change our DNA sequences, but it can change/affect our DNA sequences by changing how the body reads or interprets it

EPIGENETICS

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GENOME LEVEL
- If there are altertions:

POINT MUTATION
COPY NUMBER VARIANTS
CHROMOSOME REARRANGEMENT
ANEUPLOIDY
CHANGES IN GENE EXPRESSION

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CANCER AFFECTS 3 BASIC CELLULAR
PATHWAYS:
 Differentiation (specialization)

A. CELL FATE
B. GENOME SURVIVAL
C. GENOME MAINTENANCE

CELL FATE

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CANCER AFFECTS 3 BASIC CELLULAR
PATHWAYS:
 Ability of cells to WITHSTAND VARIOUS STRESSES and maintain their viability

A. CELL FATE
B. GENOME SURVIVAL
C. GENOME MAINTENANCE

GENOME SURVIVAL

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CANCER AFFECTS 3 BASIC CELLULAR
PATHWAYS:
 Abilities to survive in the presence
of reactive oxygen species (ROS) & toxins, to repair DNA, to maintain chromosome integrity & structure, & to correctly splice mRNA molecules.

A. CELL FATE
B. GENOME SURVIVAL
C. GENOME MAINTENANCE

GENOME MAINTENANCE

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Growth of tissue that exceeds and is not coordinated with normal tissue
They are formed as a result of abnormal cell growth and division

TUMORS (NEOPLASMS)

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TYPES OF TUMORS
- Grows in place but DOES NOT SPREAD into, or “INVADE” surrounding tissue

BENIGN TUMOR

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TYPES OF TUMORS
- Infiltrates nearby tissue, invasive & tending to RECUR AT MULTIPLE SITES
(cancer)

MALIGNANT (CANCEROUS) TUMOR)

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A tumor is cancerous, or malignant, if it infiltrates nearby tissue. Pieces of a malignant tumor can enter the bloodstream or lymphatic vessels and travel to other areas of the body, where the cancer cells “_______” the formation of new tumors.

SEED

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TYPES OF TUMORS
- Means “NOT STANDING STILL” process of spreading
- can make a cancer DEADLY, because the new growth may be in an inaccessible part of the body, or genetically distinct enough from the original, or primary, tumor that drugs that were effective early in the illness no longer work.

METASTASIS

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Abnormal growth of melanocytes (pigment-producing cells) in the skin

CUTANEOUS MELANOMA

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CUTANEOUS MELANOMA
- ___________ is often used as a guideline to recognize potential signs

 ABCDE rule
 Asymmetry
 Border irregularity
 Color variations
 Diameter (>5mm)
 Elevation (raised/elevated area)

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GENES (when mutated) CAN CAUSE CANCER:
 >100, cause cancer when they are expressed when it wouldn’t being healthy cells/is over expressed (dominant)

ONCOGENES

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Genes that normally trigger cell division are called

PROTO-ONCOGENES

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GENES (when mutated) CAN CAUSE CANCER:
 >30, cause cancer when they are deleted/inactivated (dominant)

TUMOR- SUPPRESSOR GENES

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GENES (when mutated) CAN CAUSE CANCER:
 MISMATCH MUTATIONS, allowing other mutations to persist activating oncogenes/ inactivating tumor suppressor genes

DNA REPAIR GENES

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 Most fundamental characteristic of cancer
 Cancer begins when a cell divides more frequently, or more times
 Example: A mutation in a gene that
normally halts/slows the cell cycle can lead to

LOSS OF CELL CYCLE CONTROL

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May also contribute to cancer by affecting the cell cycle

LOSS OF CONTROL OVER TELOMERE LENGTH

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 Protect chromosomes from breaking
 In humans, they consist TTAGGG repeats & normally lost from the telomere ends as a cell matures

TELOMERES (chromosome tips)

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 Enzyme responsible for maintenance of the length of telomeres

TELOMERASE

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TELOMERASE IN NORMAL CELLS:

IS TURNED OFF

TELOMERASE IN CANCER CELLS:

IS TURNED BACK ON

TYPES OF PREDISPOSITION OF CANCER  Rare, every cell has 1 GENE VARIANT that increases cancer susceptibility & a somatic mutation occurs in the cells of the affected tissue GERMLINE CANCER or SPORADIC CANCER?

GERMLINE CANCER

TYPES OF PREDISPOSITION OF CANCER Common, caused by SOMATIC MUTATIONS, affecting only NON-SEX CELLS. May result from a single dominant/2 recessive mutations in copies of the same gene GERMLINE CANCER or SPORADIC CANCER?

SPORADIC CANCER

CANCER AT THE CELLULAR LEVEL CHARACTERISTICS OF CANCER CELLS

 Oilier, less adherent  Loss of cell cycle control  Heritable  Transplantable  Dedifferentiated  Lack contact inhibition  Induce local blood vessel formation (angiogenesis)  Invasive  Increased mutation rate  Can spread (metastasize)

ORIGIN OF CANCER CELLS  Small population of cells within a tumor that possess stem cell-like properties  Have the ability to self-renewand differentiate into various cell types within the tumor, similar to normal stem cells in healthy tissues  Found in cancers of the brain, blood, and epithelium (breast, colon, and prostate)

ACTIVATION OF STEM CELLS THAT PRODUCE CANCER CELLS (cancer stem cells)

ORIGIN OF CANCER CELLS  Cells lose some of their distinguishing characteristics as mutations occur when they divide  May begin to express“stemness” genes that override signals to remain specialized

DEDIFFERENTIATION

ORIGIN OF CANCER CELLS  If a mutation renders a differentiated cell able to divide to yield other cells that frequently divide, then over time these cells may takeover, forming an abnormal growth

INCREASE IN THE PROPORTION OF A TISSUE THAT CONSISTS A STEM/PROGENITOR CELLS

ORIGIN OF CANCER CELLS  Too much repair may trigger tumor formation  If too much cells divide to fill in the space left by injured tissue, & those cells keep dividing, an abnormal growth may result

FAULTY TISSUE REPAIR

2 TYPES OF GENETIC ALTERATIONS THAT OCCUR WITHIN CANCER CELLS  Provides the selective growth advantage to a cell that defines the cancerous state  Directly contribute to the development & progression of cancer  Typically found in oncogenes/tumor suppressor genes (about 200)

DRIVER MUTATION

2 TYPES OF GENETIC ALTERATIONS THAT OCCUR WITHIN CANCER CELLS  Occurs in cancer cell, but does not directly contribute to the development/progression of cancer  Considered incidental and may arise as a consequence of the genetic instability commonly observed in cancer cells  Thousands of genes can harbor passenger mutations  Example: silent

PASSENGER MUTATION

3 STRIKES DRIVE CANCER Breakthrough: BRAF Expansion: TERT Invasion: CDK2NA, TP53, PIK3CA A. MELANOMA B. PANCREATIC CANCER C. CERVICAL CANCER D. COLORECTAL CANCER

MELANOMA

3 STRIKES DRIVE CANCER Breakthrough: KRAS Expansion: CDK2NA Invasion: SMAD4, TP53 A. MELANOMA B. PANCREATIC CANCER C. CERVICAL CANCER D. COLORECTAL CANCER

PANCREATIC CANCER

3 STRIKES DRIVE CANCER Breakthrough: TP53, RB Expansion: PIK3CA Invasion: MAPK1, STK11, FBXw7 A. MELANOMA B. PANCREATIC CANCER C. CERVICAL CANCER D. COLORECTAL CANCER

CERVICAL CANCER

3 STRIKES DRIVE CANCER Breakthrough: APC Expansion: KRAS Invasion: SMAD4, TP53, PIK3CA, FBXW7 A. MELANOMA B. PANCREATIC CANCER C. CERVICAL CANCER D. COLORECTAL CANCER

COLORECTAL CANCER

CHROMOSOME IN CANCER CELLS

Abnormal in number  Abnormal in structure

joins parts of non - homologous chromosomes can hike expression of a gene turning it into an oncogene

TRANSLOCATION

can increase the number of copies of an oncogene

DUPLICATIONS

may remove a tumor- suppressor gene

DELETION

Coined in 2011, shatters several chromosomes and may kill the cell/trigger cancer

CHROMOTHRIPSIS

3 EXAMPLES OF GENES THAT CANACTIVATE PROTO-ONCOGENES  Virus infecting a cell may insert DNA nest to a proto- oncogene  Viruses cause cervical cancer, Kaposi sarcoma A. VIRAL GENE B. A GENE ENCODING A HORMONE C. PARTS OF ANTIBODY GENES

VIRAL GENE

3 EXAMPLES OF GENES THAT CANACTIVATE PROTO-ONCOGENES - Normally very actively transcribed  Example: inversion on chromosome 11 places a proto-oncogene next to a DNA sequence that controls transcription of the parathyroid hormone gene A. VIRAL GENE B. A GENE ENCODING A HORMONE C. PARTS OF ANTIBODY GENES

A GENE ENCODING A HORMONE

3 EXAMPLES OF GENES THAT CANACTIVATE PROTO-ONCOGENES Among the most highly transcribed Examples: a) Cervical and anal cancer following HPV infection may begin when proto- oncogenes are mistakenly activated with antibody genes b) Burkitt lymphoma(cancer common in Africa): large tumor develops from lymph glands near the jaw  Proto-oncogene on chromosome 8 moves to chromosome 14, next to a highly expressed antibody gene lymph glands near the jaw  Proto-oncogene on chromosome 8 moves to chromosome 14, next to a highly expressed antibody gene A. VIRAL GENE B. A GENE ENCODING A HORMONE C. PARTS OF ANTIBODY GENES

PARTS OF ANTIBODY GENES

A PROTO-ONCOGENE MAY ALSO BE TRANSCRIBED & TRANSLATED WITH ANOTHER GENE AS IF THEY ARE ONE GENE T OR F?

TRUE

 Double gene product  Activates/lifts control of cell division  Example: ACUTE PROMYELOCYTIC LEUKEMIA

FUSION PROTEIN

Translocation between chromosomes 15 & 17 brings together a gene coding for the retinoic acid cell surface receptor & and an oncogene, myl.

ACUTE PROMYELOCYTIC LEUKEMIA

ANOTHER WAY THAT AN ONCOGENE CAN CAUSE CANCER

BY EXCESSIVE RESPONSE TO GROWTH FACTOR

Cell surface receptors for epidermal growth factor  Product of an oncogene  Affected cells of about 25%of women with breast cancer have 1 - 2 million copies of the protein

HER2 PROTEINS

HER2 PROTEINS function as a __________

TYROSINE KINASE

a monoclonal antibody, based drug

HERCEPTIN (trastuzumab)

 Normal function: Inhibit expression of genes involved in all of the activities that turn a cell cancerous  Can result to cancer when they are lost/silenced/deleted/ if the promoter regions blinds too many methyl (CH3) groups, which blocks transcription  Example: WILMS’ TUMOR

TUMOR-SUPPRESSOR GENES

 Loss of tumor suppression  Gene is deleted that normally halts mitosis in the rapidly developing kidney

WILM'S TUMOR

 Rare childhood eye tumor, occurs in about 1 in 20,000 infants  Causes: a. 1 germline mutant allele for RB1 gene in each of their cells & then cancer develops in a somatic cell where the second copy mutates (2 point mutations/deletions, 1 germline, & 1 somatic) b. Sporadic cases: 2 somatic mutations in RB1 gene, 1 on each copy of chromosome 13 Cancer starts in a cone cell of the retina (provide color vision)  Mutations in RB1 gene cause other cancers (bone, bladder, breast,

RETINOBLASTOMA (RB)

 Single gene that causes a variety of cancers when mutant (a cell with damaged DNA is permitted to divide resulting to cancer)  Occur only in somatic cells  Point mutation/deletion in the gene causes more than half of human cancers  Mediator: “the guardian of the genome”  Example: type of skin cancer caused by p53 mutation in skin cells damaged from repeated sunburns

P53 GENE

 Normal function: cellular adhesion protein found in tissue linings  When deleted, cancer results Example: FAMILIAL DIFFUSE GASTRIC CANCER

E-CADHERIN GENE

 “exon skipping” missense mutation in the E-cadherin gene that deleted an entire exon  Treatment: surgical removal of stomach (total gastrectomy)

FAMILIAL DIFFUSE GASTRIC CANCER

 2 major breast cancer susceptibility genes  Account for 15-20% of the 5% cases that are familial  Mutations in these genes is inherited in an autosomal dominant manner with incomplete penetrance

BRCA1 & BRCA2 GENES

 Risk of inheriting breast (mutations in the ends of the gene) & or ovarian cancer (mutations in the middle part of the gene)  Most common mutation: deletion of 2 adjacent DNA bases

BRCA1

 Acts as a tumor-suppressor by helping maintain genomic integrity & preventing the formation of cancerous cells  Women: 45-70% risk of breast cancer & 10-20% risk of ovarian cancer  Men: at an increased risk of breast cancer, prostate cancer, & pancreatic cancer  Other cancers: colon, kidney, gallbladder, skin,

BRCA2

ENVIRONMENTAL CAUSES OF CANCER

CHEMICAL EXPOSURES DIET TOBACCO SMOKE UV RADIATION BOTH ENVIRONMENTAL AND GENETIC FACTOR

ENVIRONMENTAL CAUSES OF CANCER  Toxic pesticides, herbicides, fungicides, fumigants (non- Hodgkin’s lymphoma tumors) A. CHEMICAL EXPOSURES B. DIET C. TOBACCO SMOKE D. UV RADIATION E. BOTH ENVIRONMENTAL AND GENETIC FACTOR

CHEMICAL EXPOSURES

ENVIRONMENTAL CAUSES OF CANCER - Vegetable-poor, meaty diet: heterocyclic aromatic amines (carcinogenic) accumulate & elevate cancer risk (colon)  Cruciferous vegetables: (broccoli & brussel sprouts): release chemical that activate enzymes detoxifying animes A. CHEMICAL EXPOSURES B. DIET C. TOBACCO SMOKE D. UV RADIATION E. BOTH ENVIRONMENTAL AND GENETIC FACTOR

DIET

ENVIRONMENTAL CAUSES OF CANCER -  Major cause of cancer (lung, mouth, throat, etc.)  2nd hand smoke exposure is also linked to an increased risk of cancer  Carcinogens: benzene, formaldehyde, & polycyclic aromatic hydrocarbons (PAHs) A. CHEMICAL EXPOSURES B. DIET C. TOBACCO SMOKE D. UV RADIATION E. BOTH ENVIRONMENTAL AND GENETIC FACTOR

TOBACCO SMOKE

ENVIRONMENTAL CAUSES OF CANCER -  Sun/artificial sources (skin cancer) A. CHEMICAL EXPOSURES B. DIET C. TOBACCO SMOKE D. UV RADIATION E. BOTH ENVIRONMENTAL AND GENETIC FACTOR

UV RADIATION

ENVIRONMENTAL CAUSES OF CANCER - Melanoma (type of skin cancer): sun exposure elevates risk, but certain gene variants (MC1R gene) known for imparting red hair, fair skin, freckles, double the risk even if the person avoids intense sunlight A. CHEMICAL EXPOSURES B. DIET C. TOBACCO SMOKE D. UV RADIATION E. BOTH ENVIRONMENTAL AND GENETIC FACTOR

BOTH ENVIRONMENTAL AND GENETIC FACTOR

CANCER DIAGNOSIS & TREATMENTS COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER:

1. MEDICAL HISTORY & PHYSICAL EXAMINATION 2. LABORATORY TESTS 3. IMAGING TESTS 4. BIOPSY 5. PATHOLOGY AND HISTOPATHOLOGY 6. STAGING

COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER: - Symptoms, risk factors, family history, & previous medical records; visible signs or abnormalities A. MEDICAL HISTORY & PHYSICAL EXAMINATION B. LABORATORY TESTS C. IMAGING TESTS D. BIOPSY E. PATHOLOGY AND HISTOPATHOLOGY F. STAGING

MEDICAL HISTORY & PHYSICAL EXAMINATION

COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER: -  Evaluate various aspects of body’s functioning  CBC, liver function tests, kidney function test, tumor markers, & genetic testing A. MEDICAL HISTORY & PHYSICAL EXAMINATION B. LABORATORY TESTS C. IMAGING TESTS D. BIOPSY E. PATHOLOGY AND HISTOPATHOLOGY F. STAGING

LABORATORY TESTS

COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER: -  VISUALIZE internal structures of the body & detect any abnormal growths/masses  X-rays, CT scans, MRI scans, ultrasound, PET scans A. MEDICAL HISTORY & PHYSICAL EXAMINATION B. LABORATORY TESTS C. IMAGING TESTS D. BIOPSY E. PATHOLOGY AND HISTOPATHOLOGY F. STAGING

IMAGING TESTS

COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER: - Removal of a sample tissue/cells from a suspicious area for lab analysis A. MEDICAL HISTORY & PHYSICAL EXAMINATION B. LABORATORY TESTS C. IMAGING TESTS D. BIOPSY E. PATHOLOGY AND HISTOPATHOLOGY F. STAGING

BIOPSY

COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER: - Examination of a tissue under a microscope A. MEDICAL HISTORY & PHYSICAL EXAMINATION B. LABORATORY TESTS C. IMAGING TESTS D. BIOPSY E. PATHOLOGY AND HISTOPATHOLOGY F. STAGING

PATHOLOGY & HISTOPATHOLOGY

COMMON STEPS & METHODS IN THE DIAGNOSTIC PROCESS FOR CANCER: - Performed once a cancer diagnosis is confirmed  Evaluating the size of the tumor, involvement of nearby lymph nodes, & presence of metastasis A. MEDICAL HISTORY & PHYSICAL EXAMINATION B. LABORATORY TESTS C. IMAGING TESTS D. BIOPSY E. PATHOLOGY AND HISTOPATHOLOGY F. STAGING

STAGING

TRADITIONAL WAYS OF TREATING CANCER - Removal of primary tumor before it has invaded healthy tissue & spread through the bloodstream A. CHEMOTHERAPY B. SURGERY C. RADIATION THERAPY

SURGERY

TRADITIONAL WAYS OF TREATING CANCER - Use of drugs to kill/inhibit the growth of cancer cells A. CHEMOTHERAPY B. SURGERY C. RADIATION THERAPY

CHEMOTHERAPY

TRADITIONAL WAYS OF TREATING CANCER - Use of high-energy radiation to target & destroy cancer cells A. SURGERY B. RADIATION THERAPY C. CHEMOTHERAPY

RADIATION THERAPY

NEW APPROACH TO DIAGNOSING & TREATING CANCER - Targeted therapy drugs designed to specifically inhibit the activity of tyrosine kinases A. GENE EXPRESSION PROFILING B. CHIMERIC ANTIGEN RECEPTORS(CAR) TECHNOLOGY C. LIQUID BIOPSY D. TYROSINE KINASE INHIBITOR

TYROSINE KINASE INHIBITOR

NEW APPROACH TO DIAGNOSING & TREATING CANCER - Specifically describe the type of cell that turns cancerous, which informs treatment choices A. GENE EXPRESSION PROFILING B. CHIMERIC ANTIGEN RECEPTORS(CAR) TECHNOLOGY C. LIQUID BIOPSY D. TYROSINE KINASE INHIBITOR

GENE EXPRESSION PROFILING

NEW APPROACH TO DIAGNOSING & TREATING CANCER - Creates DNA instructions for a hybrid surface protein (CAR) onTcells that the body does not normally synthesize A. GENE EXPRESSION PROFILING B. CHIMERIC ANTIGEN RECEPTORS(CAR) TECHNOLOGY C. LIQUID BIOPSY D. TYROSINE KINASE INHIBITOR

CHIMERIC ANTIGEN RECEPTORS(CAR) TECHNOLOGY

NEW APPROACH TO DIAGNOSING & TREATING CANCER - Checking DNA pieces in the blood plasma for oncogene/ tumor suppressor mutation  DNA detected is called cell-free/ circulating tumor DNA (ctDNA)  Detects cancer recurrence (may have new mutations)  Useful for monitoring response to treatment (if the drug is working, level of ctDNA will decrease) A. GENE EXPRESSION PROFILING B. CHIMERIC ANTIGEN RECEPTORS(CAR) TECHNOLOGY C. LIQUID BIOPSY D. TYROSINE KINASE INHIBITOR

LIQUID BIOPSY