Familial Neoplasms Flashcards
Briefly describe oncogenes and list some mutations that are examples of oncogenes.
Oncogenes have dominant effects, where only 1 allele needs to be affected to result in cancer. They have a positive effect on growth.
Examples include: RAS, cMYC, MET, CDK4, BCR-ABL, BCL2.
Briefly describe tumour suppressor genes and list some mutations that are examples of tumour suppressor genes.
Tumour suppressor genes are common in familial cancer syndromes, and are recessive, requiring a “two-hit” hypothesis, where loss of both tumour suppressor activity is required.
Examples include: retinoblastoma gene (RB1), familial breast-ovarian (BRCA1,2), familial adenomatous polyposis (APC).
Briefly describe DNA repair genes and list some mutations that are examples of DNA repair genes.
DNA repair genes are involved in repair of DNA, such as nucleotide excision repair genes to repair DNA adducts formed by carcinogens, and mismatch repair genes to “spell-check” DNA during synthesis which would otherwise result in microsatellite instability.
Examples include nucleotide excision repair genes for UV light damage in xeroderma pigmentosa and MMR genes MSH2, MLH1, MSH6 for HNPCC.
What will eventually become routine practice of genetic testing?
Next generational sequencing (NGS), a panel that assesses different categories of gene mutations.
Category 1 for highly penetrant mutations with well established risks, such as BRCA1/2, P53, MMR.
Category 2 of moderate penetrant mutations associatied with moderately increased risk of cancer.
Category 3 for newly identified genes with unyet determined characterisation and cancer risk.
What are the features and cancer risk of BRCA 1?
Features: triple negative, high grade cancer in young women.
Cancer risk: breast 60-80%, second primary in breast 60%, ovarian 20-40%.
What are the features and cancer risks of BRCA2?
Features: ER+, may occur later in life.
Cancer risk: breast 50-80%, prostate 10-20%, ovarian 10-30%, male breast 7%.
