NO P16(INK4A) CDKN2/MTS1 MUTATIONS INDEPENDENT OF P53 STATUS IN SOFT-TISSUE SARCOMAS/

The p16(INK4A)/CDKN2/MTS1 gene encodes a specific inhibitor of cyclin- dependent kinases (CDKs) 4 and 6. This study investigates p16(INK4A) g ene status and expression in mesenchymal tumours, in particular soft t issue sarcomas (STSs), Employing non-radioactive polymerase chain reac tion-single strand conformational polymorphism (PCR-SSCP) sequencing, no p16(INK4A) mutation was found in 86 samples taken from 74 mesoderma l tumours with known p53 gene status, This suggests that p16(INK4A) ge ne alterations, in contrast to p53, are not involved in the progressio n of STS, This finding is supported by the reports of a low frequency of deletions and intragenic mutations in STS, Furthermore, by immunohi stochemistry (IHC), an inverse correlation was established between p16 (INK4A) and RB positivity for 62 per cent of the frozen tumour samples investigated, However, alterations in other components of the pRb/p16 (INK4A)/CDK4/cyclin D1/E2F pathway have been proven crucial for tumour igenesis in human sarcomas. (C) 1998 John Wiley & Sons, Ltd.