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Germline mutations are frequent in the APC gene but absent in the β‐ Catenin gene in familial adenomatous polyposis patients
Author(s) -
Cao Xia,
Eu Kong Weng,
SeowChoen Francis,
Cheah Peh Yean
Publication year - 1999
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199908)25:4<396::aid-gcc13>3.0.co;2-2
Subject(s) - familial adenomatous polyposis , gene , genetics , germline , germline mutation , adenomatous polyposis coli , cancer research , biology , catenin , mutation , colorectal cancer , cancer , wnt signaling pathway
Inactivation of the adenomatous polyposis coli ( APC ) gene has been shown to initiate the majority of colorectal cancer (CRC), including a familial form called familial adenomatous polyposis (FAP). One consequence of the APC mutation is the activation of the β‐catenin ( CTNNB1 )/T‐cell transcription factor (Tcf) pathway. A recent study has shown that about half of the sporadic CRC lacking APC mutation has CTNNB1 mutation, suggesting that CTNNB1 mutation can substitute for APC mutation in the initiation of colorectal tumorigenesis. However, the frequency of CTNNB1 germline mutation in FAP has not been reported. In the present study, we investigated the frequencies of APC and CTNNB1 germline mutations in 26 unrelated FAP families. We used the Protein Truncation Test (PTT) to screen the entire coding region of APC and found germline mutations in twenty families. We then screened for CTNNB1 germline mutations in the rest of the families lacking detectable APC mutations. No missense mutations at GSK‐3β phosphorylation sites or interstitial deletion of exon 3 of CTNNB1 was found. Our results indicate that APC germline mutations are frequent but CTNNB1 germline mutations are rare in FAP patients, suggesting that CTNNB1 mutation cannot substitute for APC mutation in the initiation of FAP. Genes Chromosomes Cancer 25:396–398, 1999. © 1999 Wiley‐Liss, Inc.