Mutation spectrum of the APC gene in the Newfoundland patients with APC-associated polyposis conditions

Ma, Aihua (2007) Mutation spectrum of the APC gene in the Newfoundland patients with APC-associated polyposis conditions. Masters thesis, Memorial University of Newfoundland.

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Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant colon cancer predisposition that results from germline mutations in the adenomatous polyposis coli (APC) gene. F AP shows substantial phenotypic variability: classical FAP patients develop more than 100 colorectal adenomas, whereas those with attenuated FAP (AFAP) have fewer than 100 adenomas and those with multiple adenomas present fewer than 50 polyps. The incidence of colorectal cancer (CRC) in Newfoundland is 27% higher than the national average. However, the mutation spectrum in this population has not been well characterized. Using direct DNA sequencing and multiple ligation-dependent probe amplification (MLPA), we performed mutation scanning of the APC gene in 48 unrelated Newfoundland patients with FAP/AFAP/multiple adenomas. Three previously described and one novel truncating mutation were identified in four PAP patients (44%). Exon14 deletion was detected in one patient with AFAP (5%). Two previously known missense variants were found in 15 individuals. In addition, eight silent variants were also identified in studied patients and four of them are novel. Our results suggest: 1) the genetic predisposition to F AP in Newfoundland population is similar to that in other populations; 2) germline APC mutation may not be the major cause for AFAP; 3) the search for exonic deletion of the APC gene is necessary for mutation study on patients with AFAP.

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