Aberrant RNA splicing in the hMSH2 gene: Molecular identification of threeaberrant RNA in Scottish patients with colorectal cancer in the West of Scotland

Blood samples from 47 unselected patients with colorectal cancer were used as a source of hMSH2 mRNA, We identified three new hMSH2 aberrant mRNAs inc luding: 1) IVS15 +5 G->C resulting in exon 15 skipping from transcript; 2) an mRNA deletion of exons 2 to 6 inclusive; and 3) an mRNA deletion of exon s 2 to 8 inclusive. In order to find out whether or not exon skipping is a natural consequence of alternative mRNA splicing, total RNA from 20 healthy individuals was converted to cDNA by reverse-transcriptase polymerase chai n reaction, and our results show that none of the healthy individuals have the above aberrant mRNA, Our results also show that the presence of mutatio ns in colorectal cancer cases, which do not fully meet the hereditary non-p olyposis colon cancer criteria, would suggest that all familial cases shoul d be investigated for germ line mutations in the mismatch repair genes. (C) 2000 Wiley-Liss, Inc.