Aberrant RNA splicing in the hMSH2 gene: molecular identification of three aberrant RNA in Scottish patients with colorectal cancer in the West of Scotland

Am J Med Genet. 2000 Nov 6;95(1):49-52. doi: 10.1002/1096-8628(20001106)95:1<49::aid-ajmg10>3.0.co;2-p.

Abstract

Blood samples from 47 unselected patients with colorectal cancer were used as a source of hMSH2 mRNA. We identified three new hMSH2 aberrant mRNAs including: 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 exons 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 chain reaction, and our results show that none of the healthy individuals have the above aberrant mRNA. Our results also show that the presence of mutations in colorectal cancer cases, which do not fully meet the hereditary non-polyposis colon cancer criteria, would suggest that all familial cases should be investigated for germ line mutations in the mismatch repair genes.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Base Sequence
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • DNA Mutational Analysis
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • DNA-Binding Proteins*
  • Family Health
  • Female
  • Gene Frequency
  • Humans
  • Male
  • MutS Homolog 2 Protein
  • Mutation
  • Proto-Oncogene Proteins / genetics*
  • RNA Splicing*
  • RNA, Messenger / genetics
  • Scotland
  • Sequence Deletion

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • MSH2 protein, human
  • MutS Homolog 2 Protein