Codeletion of p15 and p16 genes in primary non-small cell lung carcinoma.
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.
Xiao
S
S
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Li
D
D
Corson
J M
JM
Vijg
J
J
Fletcher
J A
JA
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins