Cancer Genetics

Question 1

Cancer Genetics

Answer 1

Loss of function mutation in the WT1 gene on chromosome 11, which encodes for a transcription factor that is important in the control of cell growth and differentiation. Autosomal dominant inheritance.

Question 2

Two-Hit Hypothesis

Answer 2

Idea that one good tumor suppressor gene is enough for cell cycle control, so you need to lose function in both (two-hits) to get cancer

Question 3

Sporadic Cancers

Answer 3

Mutation occurs in tumor suppressor gene on one homolog in one cell. The second mutation occurs in the same gene in the same cell. Results in loss of all tumor suppressor activity which causes cancer.

Question 4

Familial Cancers

Answer 4

The first hit is inherited and present in every cell.. The second mutation can occur in any cell, resulting in cancer.

Question 5

Loss of Heterozygosity

Answer 5

Parents are homozygous at a locus, meaning that the child in heterozygous. When there is a mutation, the child becomes homozygous for the mutant and loses the heterozygosity.

Question 6

Rb Protein

Answer 6

Regulator of G1/S transition. Rb is hyperphosphorylated by cyclin/CDK, removing it from the E2Fs which activate S phase genes. It can also bind to DNA and block transcription.

Question 7

G1/S mutations

Answer 7

Virtually all cancer cells show dysregulation of one of the four genes that regulate the phosphorylation of RB (Rb, CDK4, ClnD, CDK)

Question 8

Retinoblastoma

Answer 8

Childhood cancer that results from a mutation of Rb gene on chromosome 13.

Question 9

Familial Retinoblastoma

Answer 9

Multiple tumors, bilateral in eyes, early onset

Question 10

Sporadic Retinoblastoma

Answer 10

single tumor, unilateral in eyes, and later onset

Question 11

P53

Answer 11

Tumor suppressor that controls both cell birth and cell death. It is a transcription factor that is activated by cell stress, particularly DNA damage and it controls the G1/S checkpoint.

Question 12

Li-Fraumeni Syndrome

Answer 12

Rare disorder that greatly increases the risk of cancer at a young age. Inherited mutation in p53. Autosomal dominant inheritance.

Question 13

Familial Adenomatous Polyposis

Answer 13

Multiples polyps in the colon. High penetrance, autosomal dominant inheritance. Caused by several mutations in the APC gene, indicating allelic heterogeneity.

Question 14

Hereditary Non-Polyposis Colon Cancer (HNPCC): Lynch Syndrome

Answer 14

Mutation in DNA mismatch repair genes (MMR). At least 5 genes can be responsible, but MSH2 and MLH1 are mostly responsible. Cells. Accumulate mutations quickly and tumors exhibit microsatellite instability.

Question 15

Breast/Ovarian Cancer

Answer 15

High penetrance and solid family history of cancer.

Question 16

BRCA1 and BRCA2

Answer 16

breast cancer type 1 and 2 susceptibility protein. found in the cells of breast and other tissue. Involved in DNA repair or apoptosis when DNA cant be repaired. Allelic heterogeneity.

Question 17

HER-2

Answer 17

Human Epidermal Growth factor Receptor 2. Seen in 30% of breast cancers. Form double minute chromosomes. Seen in sporadic breast cancer.

Question 18

Herceptin

Answer 18

Antibody drug that binds to HER2 and prevents binding of EGF to HER2. Decrease tumor proliferation. Good for HER2+ tumors.

Question 19

MicroRNA in Tumorigenesis

Answer 19

MiRNAs act to reduce the expression of gene by targeting specific mRNAs. A reduction of miRNA could lead to tumors or an increased of miRNA that could inhibit tumor suppressor RNA.