Unit 7 - Cancer Genetics Flashcards

Question

inherited VS sporadic mechanism of tumor suppressor gene mutation

Answer 1

remember that tumor suppressor gene mutations are recessive; need 2 mutated alleles to see tumor inherited: will have one mutated allele from affected parent - patient will have 1 somatic (sporadic) mutation in order to have cancer sporadic: patient is born normal, but along the way gets 2 different mutations

Answer 2

two mutations in the same cell are needed to start cancer - sporadic usually unilateral - inherited usually bilateral - appearance of dominance, even though gene itself is recessive

Answer 3

somatic - usually older age of onset (needs both sporadic mutations) familial - usually younger onset (only needs 1 more mutation)

Answer 4

familial cancer syndrome with inheritance of p53 mutation - p53 has no one target tissue and not specific to one disease, thus multiple neoplasia - increased risk of cancer (50% at age 30, 90% at age 70)

Answer 5

1/8 to 1/10, can be familial or sporadic, with errors in homologous recombination or DNA repair defects -2 known genes: BRCA1 (Xm 17, near NF1 and p53), BRCA2 (Xm 13, near Rb1)

Answer 6

in 80-90% of familial breast cancer (should review pedigrees to assess risk) - in 5-9% of all breast cancer - multiple mutations - increased risk of male breast cancer - increased risk in Ashkenazi Jewish population

Answer 7

type of tumor suppressor gene mutation - inability to repair DNA defects/mutations - -accumulation of abnormal DNA/genes - -increase in genome instability (breakage syndromes) - -may lead to mutations of proto-oncogenes or tumor suppressor genes - inherited or acquired

Answer 8

1. breast/ovarian cancer 2. familial polyposis coli 3. retinoblastoma 4. von Recklinghausen neurofibromatosis 5. Wilm's tumor 6. von Hippel Lindau/renal cell cancer

Answer 9

1. Fanconi anemia 2. Bloom syndrome - DNA ligase 1 or DNA helicase mutation 3. Ataxia telangiectasia 4. Xeroderma pigmentosum - excision repair 5. Cockayne syndrome - excision repair cross complementation

Answer 10

diverse group of diseases with different clinical phenotypes, and caused by genes on different Xms - recessive inheritance - Xm instability - defective DNA repair mechanisms - susceptibility to cancer

Answer 11

exchange of gene regions between sister chromatids - normal event, and in normal cells, it causes a swap of identical pieces of DNA - errors can occur with unequal changes, causing duplication of sequences on one chromatid, and deletion in others - -usually repaired in normal cells, but not if mutation in DNA repair gene

Answer 12

instead of normal linear Xm, a replication error has resulted in a Y-shaped or forked structure (end of Xm was copied again)

Answer 13

2-4% of hereditary colon cancer - 90% lifetime risk for males who inherit one mutation - 70% lifetime risk for females who inherit one mutation - -40% endometrial cancer, 10-20% urinary tract cancer, 10-20% ovarian cancer HNPCC1 - gene MSH2 HNPCC2 - gene MLH1 (with HNPCC1, 70-80% of cases) HNPCC5 - gene MSH6 (only 7-10% cases)

Answer 14

repeats of 2, 3, or 4 nucleotides that are highly polymorphic in population - these are present throughout genome, and sequencing is used in DNA fingerprinting - subject to replication error due to slippage, and mutations in mismatch repair can alter total number of repeats - presence of extra bands in putative HNPCC tumor tissue is consistent with disease diagnosis (but not a direct test)

Answer 15

HNPCC is a malfunction in a normal cellular process, that in and of itself is not deleterious -accumulation of errors eventually results in system dysfunction

Answer 16

de novo - breakage or recombination - Xm rearrangement - -duplications or deletions - -translocations or inversions - -tandem duplication of genes - -generation of supernumary Xm - gain or loss of whole Xm

Answer 17

since cancer is complex and needs more than one step, progression requires a combo of environmental and gene effects - many different mutations arise, but key principle is that they must occur within a single cell - -need gatekeeper (APC), proto-oncogene (Ras), and other tumor suppressor genes (DCC, p53) to see effect

Answer 18

normal cell may have single mutation that proliferates and generates abnormal clone (acquired change in a limited number of cells) - further Xmal changes can modify karyotype and make more clones - karyotype analysis monitors presence and evolution of clones

Answer 19

change over time in karyotype due to acquisition of different mutations - increasing complexity and numbers of Xm abnormalities are usually associated with poorer prognosis - possible to use Xm abnormalities to follow patient from diagnosis to remission and relapse

Answer 20

- detection of molecular and Xmal anomalies associated with disease - -diagnosis, prognosis - -monitor remission and relapse - -must have baseline - molecular diagnostics - cytogenetics (karyotype and FISH)

Answer 21

either karyotype or genotype - original DNA and Xm complement that is foundation for genetic constitution in all cells of body - originated in zygote

Answer 22

change in constitutional DNA or karyotype | -usually present in a single cell line (clone)

Answer 23

unique = specific diagnosis | not unique = general diagnosis

Answer 24

have 10-15x increased leukemia rate b/c third Xm 21 had RUNX1 (AML1)

Answer 25

apparent homozygosity or hemizygosity in a tissue which usually demonstrates heterozygosity - in one locus, one Xm arm, or entire Xm - doesn't mean only one allele present (can have 3 of one Xm)

Answer 26

remission: treatment suppresses disease (no clinical symptoms) relapse: Xmal or molecular abnormalities reappear

Answer 27

takes 18-24 hours, and much quicker with higher statistical significance than karyotype study

Answer 28

specifically HER-1/neu type breast cancer | -with gene amplification, responds to drug herceptin better than without gene amplification