SHORT COMMUNICATION Mutation analysis of MUTYH in Japanese colorectal adenomatous polyposis patients Keiko Taki 1,2 • Yuri Sato 1 • Sachio Nomura 1,3 • Yuumi Ashihara 1 • Mizuho Kita 1 • Ikufumi Tajima 4 • Kokichi Sugano 5 • Masami Arai 1 Ó Springer Science+Business Media Dordrecht 2015 Abstract Germline MUTYH mutations were investigated in 14 Japanese colorectal polyposis patients without germ line adenomatous polyposis coli (APC) gene mutations. Three patients had a heterozygous IVS10-2A [ G MUTYH mutation. The onset of MUTYH-associated polyposis (MAP) occurs later than that of familial adenomatous polyposis with germline APC mutation. Thus, we com- pared the carrier frequency of MUTYH IVS10-2A [ G heterozygote in the APC mutation negative cases with that in 115 controls over 70 years of age who showed no apparent clinical manifestations of cancer and claimed that they had no history of cancer at the time of enrollment. The frequency of IVS10-2A [ G heterozygote in APC germline mutation negative polyposis patients was significantly higher than control subject (p = 0.012, Chi square test). Although the sample size is still too small to conclude, the IVS10-2A [ G MUTYH heterozygote might add to the risk of developing germline APC mutation negative polyposis. Keywords MAP Á MUTYH-associated polyposis Á Adenomatous polyposis Á MUTYH Á FAP Á Colorectal polyposis APC mutation screening was performed in 41 patients referred for genetic counseling with suspicion of familial adenomatous polyposis (FAP; OMIM#175100) due to clinical findings of multiple colorectal adenomas ( [ 30 polyps) (Fig. 1A). In 14 patients, no germline APC muta- tions were detected, but 3 of them had somatic mosaicism of APC mutations confined to polyps and cancerous tissues (21 %, Table 1). Because limited information is available on MUTYH variants and their contribution to polyposis (MUTYH-associated polyposis, MAP or FAP2; OMIM #608456) in Japanese [1, 2], we investigated germline MUTYH mutations in these 14 cases. Three patients had a heterozygous IVS10-2A [ G MUTYH mutation located in the splice acceptor site of intron 10 (Figs. 1B, 2Ba), which resulted in the production of an aberrant mRNA transcript that retains intron 10 with a premature stop codon and, therefore, the formation of a truncated MUTYH protein [3]. The C-terminal domain containing a proliferating cell nuclear antigen (PCNA)-binding site and the nuclear localization signal are absent in this truncated protein [4]. Therefore, we analyzed the MUTYH mRNA extracted from the peripheral blood of patients with IVS10-2A/G genotype via reverse transcription (RT)-PCR. The primers used were the same as those used by Tao et al. [3]. In two IVS10-2A/G heterozygote patients, we detected aberrant transcripts of 329 bp (as was the case in the study by Tao et al. [3]) and Electronic supplementary material The online version of this article (doi:10.1007/s10689-015-9857-1) contains supplementary material, which is available to authorized users. & Masami Arai marai@jfcr.or.jp 1 Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan 2 Division of Bioresources, Chemical Resources Laboratory, Tokyo Institute of Technology, Yokohama, Japan 3 Department of Clinical Research, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan 4 Tajima Hospital, Agatsuma-gun, Gunma, Japan 5 Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan 123 Familial Cancer DOI 10.1007/s10689-015-9857-1