title: Transcripts with splicings of exons 15 and 16 of the hMLH1 gene in normal lymphocytes: implications in RNA-based mutation screening of hereditary non-polyposis colorectal cancer.
abstract: Germline mutations of the hMLH1 gene are estimated to account for a large fraction of kindreds affected by hereditary non-polyposis colorectal cancer (HNPCC). In a significant number of cases, hMLH1 mutations result in the expression of truncated proteins. We report here two novel alternatively spliced forms of hMLH1 mRNA in normal lymphocytes. One of these novel isoforms lacks the coding region of the gene between codons 557 and 578, corresponding to the entire exon 15. The deletion introduces a frameshift that results in a premature stop signal. The other isoform is characterised by an in-frame deletion spanning codons 578-632, corresponding to loss of the entire exon 16. Further studies are necessary to establish the biological significance of these alternative splicings. The presence of alternatively spliced hMLH1 transcripts that mimic pathogenic mutations should be taken into account in the mutational screening of the hMLH1 gene by reverse transcription-polymerase chain reaction methodologies.
authors.affiliation: Department of Oncology and Neurosciences, University Gabriele D Annunzio, Chieti, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Palmirotta
authors.forename: M C
authors.initials: MC
authors.lastname: Verì
authors.forename: M C
authors.initials: MC
authors.lastname: Curia
authors.forename: G
authors.initials: G
authors.lastname: Aceto
authors.forename: F
authors.initials: F
authors.lastname: D'Amico
authors.forename: D L
authors.initials: DL
authors.lastname: Esposito
authors.forename: P
authors.initials: P
authors.lastname: Arcuri
authors.forename: R
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: L
authors.initials: L
authors.lastname: Messerini
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Cama
authors.forename: P
authors.initials: P
authors.lastname: Battista
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005091:Exons; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D017421:Sequence Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1