Last update: 05/06/2006

Background to disease

MEN 2A, MEN2B and FMTC are familial cancer syndromes displaying an autosomal dominant mode of inheritance. Classification is based on clinical phenotype:

MEN 2A – (OMIM 17140) – Families with MTC and phaeochromocytoma, parathyroid disease or both.

MEN 2B – (OMIM 16230) – Families with MTC with /without phaeochromocytoma plus other characteristic clinical abnormalities-parathyroid disease usually absent

FMTC – (OMIM 17140) – Families with at least 4 members affected with MTC and no evidence      of phaeochromocytoma / parathyroid disease.

All three syndromes are due to activating mutations in the RET (REarranged during Transfection) proto- oncogene located at Ch. 10q11.2. The gene consists of 20 exons spanning 80kb of genomic DNA. One mutation in the RET gene is sufficient for neoplastic transformation to occur.

Mutation screening is facilitated by the fact that mutations in relatively few exons account for a large percentage of MEN 2A, MEN 2B and FMTC cases:

MEN 2A – 95% of  Mutations occur at 5 cysteine residues (87% occur at codon 634)

MEN 2B – 93% of cases show a point mutation causing a substitution methionine by threonine at codon 918

FMTC – mutations in exons 10 and 11 are detected in ~ 85 % of FMTC cases.  Mutations are roughly evenly distributed between codons 618, 620 and 634

Laboratory Analysis

Contact scientist: Ian Berry

User Guide Editor: Dr Ruth Charlton PhD DipRCPath. Copyright © 2007 . Yorkshire Regional DNA Laboratory. All rights reserved.