Mutations in the p16(INK4)/MTS1/CDKN2, p15(INK4B)/MTS2, and p18 genes in primary and metastatic lung cancer

Okamoto, A., Hussain, S. P., Hagiwara, K., Spillare, E. A., Rusin, M. R., Demetrick, D. J., Serrano, M., Hannon, G. J., Shiseki, M., Zariwala, M., Xiong, Y., Beach, D. H., Yokota, J., Harris, C. C. (1995) Mutations in the p16(INK4)/MTS1/CDKN2, p15(INK4B)/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer Research, 55 (7). pp. 1448-1451. ISSN 00085472 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/7882351

Abstract

We examined the genomic status of cyclin-dependent kinase-4 and -6 inhibitors, p16(INK4), p15(INK4B), and p18, in 40 primary lung cancers and 31 metastatic lung cancers. Alterations of the p16(INK4) gene were detected in 6 (2 insertions and 4 homozygous deletions) of 22 metastatic non-small cell lung cancers (NSCLCs; 27%), but none were detected in 25 primary NSCLCs, 15 primary small cell lung cancers (SCLCs), or 9 metastatic SCLCs, indicating that mutation in the p16(INK4) gene is a late event in NSCLC carcinogenesis. Although three intragenic mutations of the p15(INK4B) gene were detected in 25 primary NSCLCs (12%) and five homozygous deletions of the p15(INK4B) gene were detected in 22 NSCLCs (23%), no genetic alterations of the p15(INK4B) gene were found in primary and metastatic SCLCs. The p18 gene was wild type in these 71 lung cancers, except 1 metastatic NSCLC which showed loss of heterozygosity. We also examined alterations of these three genes and expression of p16(INK4) in 21 human lung cancer cell lines. Alterations of the p16(INK4) and p15(INK4B) genes were detected in 71% of the NSCLC cell lines (n = 14) and 50% of the NSCLC cell lines (n = 14), respectively, but there were mine in the 7 SCLC cell lines studied. No p18 mutations were detected in these 21 cell lines. These results indicate that both p16(INK4) and p15(INK4B) gene mutations are associated with tumor progression of a subset of NSCLC, but not of SCLC, and that p15(INK4B) mutations might also be an early event in the molecular pathogenesis of a subset of NSCLC.

Item Type: Paper
Uncontrolled Keywords: cyclin dependent kinase protein kinase inhibitor DNA article gene deletion gene expression gene mutation homozygosity human human cell lung non small cell cancer lung small cell cancer metastasis oncogene polymerase chain reaction priority journal single strand conformation polymorphism tumor growth cell culture DNA sequence genetic polymorphism genetics lung tumor molecular genetics nucleotide sequence small cell carcinoma Base Sequence Carcinoma, Non-Small-Cell Lung Carcinoma, Small Cell DNA, Neoplasm Lung Neoplasms Molecular Sequence Data Polymorphism (Genetics) Sequence Analysis, DNA Support, Non-U.S. Gov't Tumor Cells, Cultured
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
organism description > animal > mammal > primates > hominids > human
diseases & disorders > cancer > cancer types > lung cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Beach lab
CSHL labs > Hannon lab
Depositing User: Jessica Koos
Date Deposited: 11 Aug 2014 20:26
Last Modified: 11 Aug 2014 20:26
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30628

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving