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Codeletion of p15 and p16 Genes in Primary Non-Small Cell Lung Carcinoma¹

Department of Pathology, Brigham and Women's Hospital [S. X., J. M. C., J. A. F.], and Gerontology Division. Beth Israel Hospital, and Division on Aging [D. L., J. V.], Harvard Medical School, Boston, Massachusetts 02115

Chromosome band 9p21 is deleted frequently in non-small cell lung carcinoma (NSCLC), and the p15 and p16 cyclin-dependent kinase-4 inhibitor genes map within this deletion region. Recent studies demonstrated deletion of p15 and p16 in NSCLC metastases and cell lines, suggesting a role for these genes in NSCLC progression. We now report p15 and p16 copy number, as determined by fluorescence in situ hybridization with a P1 contig, in 18 primary NSCLCs. Codeletion of p15 and p16 was found in 15 of 18 NSCLCs, and 1 of the 3 tumors with normal p15 and p16 copy number had a nonsense mutation in exon 2 of p16. We conclude that p15 and p16 are deleted and/or mutated in most primary NSCLCs. Two observations, however, support the involvement of at least one additional tumor suppressor gene on chromosome 9. These observations are: (a) the large size (> 100 kb) of most NSCLC p15/p16 deletions; and (b) the absence of exon 2 mutations in most retained NSCLC p15 and p16 alleles.

¹ This work was supported by NIH Grant 1K11CA01498-05 (J. A. F.) and by a Grant from Toyobo Co., Ltd., Osaka, Japan (D. L. and J. V.).

² To whom requests for reprints should be addressed, at Department of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.

Received 5/ 4/95. Accepted 6/ 2/95.

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