Japanese Journal of Clinical Oncology 32:215-218 (2002)
© 2002 Foundation for Promotion of Cancer Research
A Novel Germline Mutation of hMLH1 in a Patient with Hereditary Non-polyposis Colorectal Cancer
1 Department of Surgery, Hoshi General Hospital, Fukushima, 2 Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsonomiya and 3 Department of Second Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
DNA mismatch repair genes, hMLH1 and hMSH2, assigned on chromosome 3p21–23 and 2p21–22 are involved in hereditary non-polyposis colorectal cancer (HNPCC). The heterozygous carrier of the mutated allele results in a mutator phenotype and accelerating tumorigenesis, which especially causes carcinomas in the gastrointestinal and genitourinary tracts. We screened germline mutations of mismatch repair genes hMLH1 and hMSH2 in a patient with multiple primary neoplasms (multiple stomach cancers, colon cancer and brain tumor) in a cancer clustered HNPCC family. Screening by long RT-PCR from the RNA extracted from puromycin-treated heparinized blood showed skipping of the exon 2 in hMLH1. The analysis of the genomic DNA showed a GT deletion in the splice-donor site of the exon 2, which is compatible with the splicing variant detected by long RT-PCR analysis. This is a novel germline mutation that has not been reported previously.
+ For reprints and correspondence: Kenji Gonda, Department of Surgery, Hoshi General Hospital, Omathi 2–1–16, Koriyama, Fukushima 963-8501, Japan. E-mail: nomizu@hoshipital.or.jp