Cancer Genetics Flashcards
1
Q
Oncogenes
A
- mutations are gain of function
- provide a persistent proliferative signal
- usually dominant
2
Q
Tumor suppressor genes
A
- mutations are loss of function
- gatekeeper tumor suppressors: control cell cycle
- caretaker tumor suppressors: protect the integrity of the genome
- recessive
3
Q
Mutations that can turn a proto-oncogene into an oncogene
A
- hyperactive protein made in normal amounts
- normal protein greatly overproduced
- nearby regulatory DNA sequence causes the normal protein to be overproduced
- fusion to actively transcribed gene produces hyperactive fusion protein
4
Q
HER2/Neu
aka ERBB2
A
- member of the epidermal growth factor receptor family
- mutations are common in sporadic breast cancer
- point mutations create a constitutively active protein
- oncogene
5
Q
Myc
A
- 3 members: c-myc (rapidly proliferating cells), N-myc (pre-B cells, kidney, brain and intestine), and L-myc (embryogenesis and in kidney and lung)
- transcription factors with roles in controlling cell cycle progression, apoptosis and trasformation
- upregulates cyclins, downregulates p21, downregulates Bcl-2
- hyperactive myc associated with many types of cancer
- N-myc specifically with neuroblastoma
- oncogene
6
Q
Burkitt’s Lymphoma
A
- chromosomal translocation t(8;14)
- fuses IgH and Myc
- B cells have high expression of IgH -> when fused leads to high expression of myc -> lymphoma
- fastest growing human tumor
- associated with EBV and malaria
7
Q
BCR-ABL
Philadelphia chromosome
A
- t(9;22)
- fusion of BCR (breakpoint cluster region) with ABL kinase
- associated with chronic myelogenous leukemia (CML)
- oncogene
8
Q
Examples of tumor supressors
A
Rb, p53, BRCA1/BRCA2, MLH1, MSH2
9
Q
Oncomirs
A
- microRNAs that regulate the expression of either tumor suppressors or oncogenes
10
Q
Features that suggest hereditary cancer
A
- early onset of cancer
- multiple primary cancers
- bilateral cancer
- clustering in relatives
- occurrences in multiple generations
- unusual presentation or histology
11
Q
Multiple endocrine neoplasia (MEN)
A
- inherited cancer of endocrine glands
- autosomal dominant
- type 1: MEN1 gene is mutated -> tumor suppressor that regulates genes involved in cell proliferation
- type 2: RET gene is mutated -> oncogene that gives persistent proliferative signal
- 100% risk if inherited
12
Q
Li-Fraumeni Syndrome
A
- rare, associated with a variety of cancers including breast, brain, leukemia, sarcoma, adrenal
- mutation in p53
- 90% risk if inherited
13
Q
Retinoblastoma
A
- cancer of retina
- mutations in RB1
- 99% risk if inherited
14
Q
Von Hippel-Lindau Syndrome
A
- predisposed to variety of tumors including eye, brain, spinal cord, kidney, pancreas, and adrenal
- mutation in tumor suppressor VHL which contains a ub E3 ligase activity and is involved in the degradation of HIF1
- VHL inhibits formation of blood vessels -> gives rise to highly vascularized tumors
- 40% risk if inherited
15
Q
Hereditary breast/ovarian cancer syndrome
A
- mutations in BRCA1/BRCA2
- tumor suppressor genes that encode proteins onvolved in the repair of damaged DNA
- 85% risk if inherited
