Common Hereditary Cancer Syndromes

What gene mutations are associated with Lynch syndrome?

Mismatch repair genes: MSH2, MLH1, MSH6, PMS2. Associated cancers: Colorectal cancer, Endometrial cancer, Ovarian cancer.

What is the defective mechanism in Lynch syndrome?

Defective DNA mismatch repair → microsatellite instability → increased cancer risk.

Which gene is mutated in Familial Adenomatous Polyposis (FAP)?

APC gene. Associated findings: Colorectal cancer, Desmoid tumors, Osteomas, Brain tumors.

What syndrome is caused by VHL mutation?

von Hippel-Lindau syndrome. Associated tumors: Hemangioblastomas, Clear cell renal cell carcinoma, Pheochromocytoma.

What gene is mutated in Li-Fraumeni syndrome?

TP53. Associated cancers: Sarcomas, Breast cancer, Brain tumors, Adrenocortical carcinoma, Leukemia.

What tumors are seen in MEN1 syndrome?

Mutation: MEN1 gene. Tumors: Parathyroid adenomas, Pituitary adenomas, Pancreatic endocrine tumors. Mnemonic: '3 Ps' Parathyroid, Pituitary, Pancreas.

What mutation is seen in MEN2 syndrome?

RET proto-oncogene mutation. Associated tumors: Medullary thyroid carcinoma, Pheochromocytoma, Parathyroid hyperplasia.

What is the inheritance pattern of most hereditary tumor suppressor syndromes?

Autosomal dominant. First hit inherited, Second hit → loss of remaining normal allele → cancer. This is called: Loss of heterozygosity.

Which hereditary cancer syndrome is caused by a proto-oncogene activation?

MEN2 syndrome. Gene: RET. Mechanism: Gain-of-function mutation in proto-oncogene.

Which hereditary cancer syndromes involve tumor suppressor gene inactivation?

Lynch syndrome, FAP, VHL, Li-Fraumeni, MEN1. Mechanism: Loss-of-function mutation. Often follows the 'two-hit hypothesis'.