20.06.08 Other cancer syndromes

Question 1

What is MEN (multiple endocrine neoplasia) syndrome

Answer 1

• Occurrence of tumours involving two or more endocrine glands within a single patient.
• 4 subtypes MEN1, 2, 3, 4

Question 2

Review of MEN1 (multiple endocrine neoplasia type 1)

Answer 2

• AD, LOF mutations in MEN1
• MEN1 is a tumour suppressor (repressing cell proliferation)
• 1 in 30,000
• Tumours of parathyroid
• 90% cases are familial (with variable penetrance in interfamilial heterogeneity)
• Sporadic forms less likely to test positive (due to somatic mosaicism)

Question 3

Review of MEN2 (multiple endocrine neoplasia type 2)

Answer 3

• AD, GOF mutations in RET
• RET is an proto-oncogene
• 1 in 25,000
• Medullary thyroid cancer in association with phaeochromocytoma and parathyroid tumours.

Question 4

Review of MEN4 (multiple endocrine neoplasia type 4)

Answer 4

• AD, LOF mutations in CDKN1B
• Parathyroid tumours
• Rare
• CDKN1B protein p27, regulates cell cycle progression from G1 to S phase.

Question 5

Review of VHL (von Hippel-Lindau disease)

Answer 5

• AD, LOF in VHL
• VHL is a tumour suppressor
• Hemangioblastomas (retinal, cerebellum, spinal), renal and pancreatic cysts, clear cell renal cell carcinoma, phaeochromocytoma

Question 6

Review of Basal cell nevus syndrome

Answer 6

• Deletion of 9q22.3, encompasses PTCH1
• Triad of basal cell carcinoma, keratocysts and bifid ribs.
• PTCH1 is the transmembrane receptor for morphogene SHH (Sonic hedgehog). Involved in embryonic development, cell growth and differentiation.

Question 7

Review of Birt-Hogg-Dubé syndrome

Answer 7

• AD FLCN mutations. Tumour suppressor. LOF.

- Triad: skin lesions, lung cysts and spontaneous pneumothorax, renal tumours.

Question 8

Review of Peutz-Jeghers syndrome

Answer 8

• AD, LOF mutations in STK11
• 50% cases are familial
• Tumour suppressor (serine/threonine kinase), helps cell cycle arrest and growth suppression.
• gastrointestinal polyposis, mucocutaneous pigmentation, cancer predisposition (intestinal and other epithelial forms).

Question 9

Review of Cowden syndrome

Answer 9

• AD. LOF mutations in PTEN
• Tumour suppressor. Regulates PI3K/Akt/mTOR pathway and MAPK pathway.
• 1 in 200,000
• Multiple hamartoma, macrocephaly, trichilemmomas (benign tumour of hair follicle), ID
• mTOR inhibitors are in development for these patients.