Quantitative differences between aberrant transcripts which occur as common isoforms and due to mutation-based exon skipping of the mismatch repair gene hMLH1

About one-third of hereditary non-polyposis colorectal cancer-related mutat ions in the mismatch repair gene hMLH1 result in the loss of entire exons f rom the wild type transcripts. Here we describe quantitative differences of hMLH1 transcripts without exon 15, exon 16 or exon 17 in several members o f a family with hereditary non-polyposis colorectal cancer. The transcript lacking exon 15 is caused by a G to A transition affecting the last nucleot ide of the respective exon and results in a truncated protein. The transcri pts lacking exon 16 or exon 17, which are in-frame deletions, were also fou nd in all tested samples of a normal population and represent common isofor ms. Reverse transcription-polymerase chain reaction-based relative quantifi cation revealed about 50 % signal intensity for the mutation-based transcri pt, but less than 10 % for the common isoforms, if compared to the wild typ e. All aberrant transcripts were detected from blood-derived cDNAs but not from samples of normal colon epithelium. Although the biological significan ce of the common isoforms is unknown, they might lead to false risk assessm ent in hereditary non-polyposis colorectal cancer cases.