Flashcards in Cancer Genetics Deck (19):
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.
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
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.
The first hit is inherited and present in every cell.. The second mutation can occur in any cell, resulting in cancer.
Loss of Heterozygosity
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.
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.
Virtually all cancer cells show dysregulation of one of the four genes that regulate the phosphorylation of RB (Rb, CDK4, ClnD, CDK)
Childhood cancer that results from a mutation of Rb gene on chromosome 13.
Multiple tumors, bilateral in eyes, early onset
single tumor, unilateral in eyes, and later onset
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.
Rare disorder that greatly increases the risk of cancer at a young age. Inherited mutation in p53. Autosomal dominant inheritance.
Familial Adenomatous Polyposis
Multiples polyps in the colon. High penetrance, autosomal dominant inheritance. Caused by several mutations in the APC gene, indicating allelic heterogeneity.
Hereditary Non-Polyposis Colon Cancer (HNPCC): Lynch Syndrome
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.
High penetrance and solid family history of cancer.
BRCA1 and BRCA2
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.
Human Epidermal Growth factor Receptor 2. Seen in 30% of breast cancers. Form double minute chromosomes. Seen in sporadic breast cancer.
Antibody drug that binds to HER2 and prevents binding of EGF to HER2. Decrease tumor proliferation. Good for HER2+ tumors.