The gene for the cyclin-dependent-kinase-4 inhibitor, CDKN2A, is preferentially deleted in malignant mesothelioma.

Cytogenetic deletions of the short arm of chromosome 9, 9p, have been detected in cell lines of malignant mesothelioma as well as in tumor material. Many tumor types carry deletions of chromosome 9 or more specifically of 9p21. The tumor-suppressor genes, CDKN2A and CDKN2B, each of which encodes a structurally and functionally similar cyclin-dependent kinase inhibitor, were mapped to the commonly deleted region. The tumor-suppressive effect of these genes, or of CDKN2A alone, requires functional retinoblastoma protein, pRb. Malignant mesothelioma expresses pRb, which, together with the cytogenetic data, suggests the involvement of CDKN2A and/or CDKN2B in its tumorigenesis. We present data on the deletion status of chromosome 9 in malignant mesothelioma cell lines and tumor tissue. A deletion map of the 9p21.3-p23 region was constructed for 12 cell lines. Homozygous deletions of chromosomal regions containing CDKN2A were detected in all cell lines. The smallest region of overlap for deletion is approximately 24 kb, and does not include CDKN2B. The frequency of deletion of the centromeric region of chromosome 9 was compared with that of chromosomes 1, 6, and 10 by genomic in situ hybridization. Deletion of the centromere of chromosome 9 is the predominant event at a frequency of 73 +/- 3%. Our data show that deletions of a critical region of chromosome 9, including the CDKN2A but not the CDKN2B locus, are common among malignant mesothelioma. Such deletions may be involved in tumorigenesis of mesothelium.