A novel germline mutation of hMLH1 in a patient with hereditary non-polyposis colorectal cancer.
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.
Gonda
Kenji
K
Department of Surgery, Hoshi General Hospital, Koriyama, Fukushima, Japan. nomizu@hoshipital.or.jp
Nomizu
Tadashi
T
Fukayama
Noriko
N
Sugano
Kokichi
K
Takenosita
Seiichi
S
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics; D002352:Carrier Proteins; D003110:Colonic Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1