molecular - hereditary cancer syndromes

hereditary cancer syndrome

specific, identifiable germline variant that increases risk of malignant neoplasms, often inherited from parents, can be passed to offspring, most have incomplete penetrance and variable expressivity

hereditary breast and ovarian cancer syndrome (HBOC)

BRCA1 and 2; DNA mismatch repair proteins, loss of function variants, autosomal dominant

familial adenomatous polyposis

APC; Wnt pathway protein that attenuates proliferative signal of beta catenin, loss of function variants, autosomal dominant; thousands of polyps in colon, classical and attenuated

MUTYH-associated polyposis

MUTYH; base excision repair protein, loss of function or reduced expression variants, autosomal recessive; few polyps

lynch syndrome

HNPCC, MLH1, MSH2, MSH6, PMS2; DNA mismatch repair proteins, loss of function variants, autosomal dominant; screen for with tumor microsatellite instability testing, strongly associated with endometrial cancer

hereditary diffuse gastric cancer syndrome

CDH1; cell-cell adhesion protein, loss of function variants, autosomal dominant; associated with breast and ovarian cancer, about 70% lifetime gastric cancer risk

nevoid basal cell carcinoma syndrome

PTCH1; receptor for SHH, loss of function variants, autosomal dominant; epidermal cance3r that frequently occurs on the face, may exhibit broader syndrome with odontogenic cysts, plantar pits, rib abnormalities

xeroderma pigmentosum

9 genes of XP family, DNA repair proteins, autosomal recessive, loss of function variants; severe sensitivity to sunlight, 100% risk of skin cancer, reduces life expectancy

heritable retinoblastoma

rare type of childhood eye cancer, RB1; G!-S checkpoint, autosomal dominant, loss of function variants; high cure rate

multiple endocrine neoplasia type 1

MEN1; function unclear, autosomal dominant, pancreatic, pituitary, parathyroid tumors

multiple endocrine neoplasia type 2

RET; receptor/tyrosine kinase, gain of function variants, autosomal dominant, pheochromocytoma, medullary thyroid, parathyroid tumors, LE about 50 years

cowden syndrome

PTEN; tumor suppressor gene in mTOR pathway, variants lead to increased cell proliferation, autosomal dominant; primary manifestation is development of benign hamartomas

li-fraumeni syndrome

P53; critical cell cycle control protein, autosomal dominant, loss of function variants; high risk of breast cancer, sarcomas, glioblastomas, leukemia, and adrenal tumors

von hippel-lindau syndrome

VHL; attenuates pro-proliferation transcription factor HIF1a, loss of function, autosomal dominant; hemangioblastomas are characteristic, LE about 50