50. Hereditary cancer syndromes - general characteristics. Multiple endocrine neoplasia. Familial melanoma. Retinoblastoma · Genetics · MU Sofia

50. Hereditary cancer syndromes - general characteristics. Multiple endocrine neoplasia. Familial melanoma. Retinoblastoma.

Covers MEN1 and MEN2 with their genes, protein and RET activation pathways, the MEN2A, MEN2B and FMTC subtypes in a comparison table, and the clinical features of each. Then describes familial melanoma through CDKN2A and its cell cycle role, and retinoblastoma through RB1, the two-hit model, hereditary versus sporadic forms, and diagnosis and management.

Inside: 4 sections · 6 labelled pictures · 1 table · 16 flashcards · 3 min

Topic 50 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 4 sections, about 464 words (3 min of reading), with 16 flashcards.

I. MULTIPLE ENDOCRINE NEOPLASIA (MEN)

Multiple Endocrine Neoplasia (MEN) is a group of autosomal dominant hereditary cancer syndromes characterized by the development of tumors in multiple endocrine glands.

MEN syndromes are divided mainly into MEN type 1 and MEN type 2.

MEN TYPE 1 (Wermer Syndrome)

Genetic Basis

Gene: MEN1
Chromosome: 11q13
Protein: Menin (tumor suppressor)

Normal Function of Menin

Menin regulates:

cell cycle control,
transcription,
DNA repair.

Loss of menin leads to uncontrolled endocrine cell proliferation.

Pathogenesis of MEN1

1. Germline mutation in one MEN1 allele.
2. Second somatic hit in endocrine tissues.
3. Loss of tumor suppressor function.
4. Development of multiple endocrine tumors.

Clinical Features – “3 Ps”

Parathyroid adenomas → hyperparathyroidism (most common)
Pancreatic neuroendocrine tumors (gastrinoma, insulinoma)
Pituitary adenomas (prolactinoma common)

MEN TYPE 2

Genetic Basis

Gene: RET proto-oncogene
Chromosome: 10q11
Mutation type: activating (gain-of-function)

MEN2 Subtypes

Pathogenesis of MEN2

1. Activating mutation of RET.
2. Constitutive tyrosine kinase signaling.
3. Continuous cell proliferation.
4. Early tumor development, especially in thyroid C-cells.

Key Clinical Points

Medullary thyroid carcinoma (MTC) is the hallmark.
Prophylactic thyroidectomy is life-saving.
Tumors arise from neural crest–derived cells.