Mutational analysis of N-ras, p53, p16(INK4a), p14(ARF) and CDK4 genes in primary human malignant mesotheliomas

Nineteen specimens from primary human malignant mesotheliomas obtained from 19 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 by combined RFLP-PCR/SSCP analysis. In addition, all tumours were screened for deletions and point mutations in the tumour suppressor g enes p53, p16(INK4a) (CDKN2A) and p14(ARF) (exon-1 beta) by combined multip lex-PCR/SSCP analysis. No mutations were found in N-ras, p53 and CDK4. Thre e tumours displayed homozygous deletion (co-deletion of exons 1, 2 and 3) o f p16(INK4a). One of them displayed additional homozygous deletion of p14(A RF) (exon-1 beta). Two silent point mutations and 2 polymorphisms were foun d in p16(INK4a) in 3 tumours. Our preliminary data indicate that disarrange ment of the Rb1 pathway may be involved in mesothelioma formation.