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Germline MYH mutations in a clinic‐based series of Canadian multiple colorectal adenoma patients
Author(s) -
Croitoru Marina E.,
Cleary Sean P.,
Berk Terri,
Di Nicola Nando,
Kopolovic Ilana,
Bapat Bharati,
Gallinger Steven
Publication year - 2007
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20724
Subject(s) - mutyh , medicine , germline mutation , germline , mutation , compound heterozygosity , allele , gene , colorectal adenoma , genetics , cancer research , colorectal cancer , biology , cancer
Objectives MYH is a member of the DNA base excision repair (BER) pathway and mutations of this gene predispose to the development of colorectal neoplasia in an autosomal recessive transmission pattern. Our objective was to determine the significance of MYH mutations in a series of Canadian patients with multiple adenomas. Methods We screened for germline MYH mutations (by dHPLCO) in 20 clinic‐based multiple adenoma patients who were adenomatous polyposis coli (APC) mutation‐negative. Suspected mutations were confirmed by sequence analysis. Results Six of 20 (30%) patients carried pathogenic biallelic MYH mutations, 1 Y165C homozygote and 5 compound heterozygotes of other sequence variants. We identified three novel variants, Q377X, 1314delA, and P281L, which are likely pathogenic. Twenty‐nine relatives of the Y90X/1103delC compound heterozygous carrier were also screened for germline MYH mutations, and 1 homozygous and 14 heterozygous carriers were identified. Conclusions Among patients with multiple adenomas, biallelic MYH mutations account for approximately 30% of APC mutation negative cases and two thirds of these carry mutations other than the “common” Y165C and G382D variants. Clinical screening algorithms which focus only on the Y165C and G382D alleles are inadequate since additional pathogenic mutations may be identified by screening the entire gene. J. Surg. Oncol. 2007; 95: 499–506. © 2007 Wiley‐Liss, Inc.