Gene alterations at the CDKN2A (p16/MTS1) locus in soft tissue tumors.

The CDKN2A gene (p16/MTS1) is a tumor suppressor that is frequently deleted, mutated, or inactivated by transcriptional silencing in certain tumor types and many tumor cell lines. We analyzed CDKN2A gene mutations and the frequency of loss of heterozygosity (LOH) at the CDKN2A locus in 135 soft tissue sarcomas. PCR-SSCP analysis of exons 1 and 2 of CDKN2A gene revealed only one missense mutation in codon 15 in a rhabdomyosarcoma. LOH-analysis was performed with two polymorphic markers in the surrounding regions of the CDKN2A gene (D9S171, D9S162) and the sequence-tagged-site marker c5.1. An allelic loss was found in 7/135 cases (5.1%) and was a characteristic of poorly differentiated sarcomas. We observed a high frequency of microsatellite instability expressed as allelic imbalances (25%). Presumably, alterations of the CDKN2A gene do not contribute to the oncogenesis in the majority of soft tissue tumors.