cancer as a genetic disease

Question 1

germline mutation using BRCA tumour suppressor genes: biochemical effect

Answer 1

inherited predisposition to breast and ovarian cancer; germline mutation in BRCA 1/2 (tumour suppressor) genes; DNA repair impaired (failure to repair double-stranded DNA breaks)

Question 2

germline mutation using BRCA tumour suppressor genes: clincal effect

Answer 2

earlier onset age; increase ovarian cancer risk; BRCA 2 predisposes males to breast cancer

Question 3

germline mutation using BRCA tumour suppressor genes: complications

Answer 3

some cases have family history but BRCA not affected (could be due to other monogenes); many cases show no family history (could be polygenic)

Question 4

colorectal cancer: familial adenomatous polyposis (FAP)

Answer 4

100% lifetime cancer risk (many polyps in colon each with high malignancy potential); chromosome 5: autosomal dominant shows it is clearly hereditary; chromosome 1: autosomal recessive, unknown (doesn’t appear hereditary)

Question 5

colorectal cancer: HNPCC (lynch syndrome)

Answer 5

80% cancer lifetime risk; chromosome 2 and 3: autosomal dominant; DNA mismatch repair genes mutated

Question 6

chronic myeloid leukaemia: biochemical effect (Philadelphia chromosome), treatment, consequences and monitoring methods

Answer 6

mutation: t(9,22); BCR-ABL1 fusion protein; produces specific tyrosine kinase (ATP binding site inhibited by drug); may lose response and require 2nd inhibitor so monitored by G-bonding

Question 7

chronic myeloid leukaemia: clinical effect

Answer 7

increase mature granulocyte production; elderly; chronic (benign)→accelerated (ominous)→blaso crisis (fatal)

Question 8

acute myeloid leukaemia: biochemical effect and treatment

Answer 8

abnormal accumulation of promyelocytes (granulocyte precursor); mutation: t(15,17)(q22,q12); RARa on chromosome 17 regulates DNA transcription; RARa and DML on chromosome 15 both bind too strongly, blocking transcription and differentiation; ATRA therapy dissociates co-repressors

Question 9

pharmacogenomic definition

Answer 9

study of the influence of genetic variation on drug response

Question 10

pharmacogenomic aim

Answer 10

plan chemotherapy; identify patients likely to respond to treatment using assay to detect presence/absence of somatic mutations