Somatic mutation of a candidate tumour suppressor MGA gene and its mutational heterogeneity in colorectal cancers.
Sir, The MYC protooncogene up regulates expression of cell growth and cell cycle related genes and promotes oncogenesis. Heterodimerisation of MAX with MYC activates and mediates transcription activity. MGA binds to MAX and inhibits MYC dependent cell transformation. Mutational profiling of lung adenocarcinoma genomes revealed somatic loss of function mutations of MGA, mostly nonsense mutations. Also, an inactivating mutation of MGA was found in small cell lung cancers. These data indicate that MGA could be a tumour suppressor gene (TSG) and that its inactivating mutations may contribute to solid tumour development. However, the mutation status of MGA remains unclear in most carcinomas. In colorectal cancer (CRC) one of the major ways in which APC acts as a TSG is by inhibiting degradation of free beta catenin, which then binds to TCF/ LEF, leading to consequent binding to the MYC promoter and causing up regulation of MYC. There are mononucleotide repeats in the MGA coding sequence that could be mutational targets for frameshift mutation in cancers with microsatellite instability (MSI) such as CRCs. In this study, we analysed the A7 repeats in exons 11 and 21 in 89 CRCs with high MSI (MSI H) and 45 microsatellite stable/low MSI (MSS/MSI L) CRCs by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) assay, as described previously. There was no family history of Lynch syndrome in these patients. None of the CRC cases met the minimum requirement for a clinical diagnosis of Lynch syndrome based on the Amsterdam II criteria. The MSI evaluation system used five mononucleotide repeats (BAT25, BAT26, NR 21, NR 24
Pathology