| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255 [A. O., S. P. H., K. H., E. A. S., M. R. R., C. C. H.]; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 [D. J. D., M. S., G. J. H., D. H. B.]; National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan [M. S., J. Y.]; and The University of North Carolina, Chapel Hill, North Carolina 27599-3280 [M. Z., Y. X.]
We examined the genomic status of cyclin-dependent kinase-4 and -6 inhibitors, p16INK4, p15INK4B, and p18, in 40 primary lung cancers and 31 metastatic lung cancers. Alterations of the p16INK4 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 p16INK4 gene is a late event in NSCLC carcinogenesis. Although three intragenic mutations of the p15INK4B gene were detected in 25 primary NSCLCs (12%) and five homozygous deletions of the p15INK4B gene were detected in 22 NSCLCs (23%), no genetic alterations of the p15INK4B 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 p16INK4 in 21 human lung cancer cell lines. Alterations of the p16INK4 and p15INK4B 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 none in the 7 SCLC cell lines studied. No p18 mutations were detected in these 21 cell lines. These results indicate that both p16INK4 and p15INK4B gene mutations are associated with tumor progression of a subset of NSCLC, but not of SCLC, and that p15INK4B mutations might also be an early event in the molecular pathogenesis of a subset of NSCLC.
1 This work was supported in part by a grant from the Japanese Overseas Cancer Fellowship of the Foundation for Promotion of Cancer Research (to A. O.).
2 To whom requests for reprints should be addressed, at Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg. 37, Room 2C01, Bethesda, MD 20892-4255.
Received 1/12/95. Accepted 2/20/95.
This article has been cited by other articles:
|
|
 |
|
  S Mohamed, K Yasufuku, T Nakajima, K Hiroshima, R Kubo, A Iyoda, S Yoshida, M Suzuki, Y Sekine, K Shibuya, et al. Analysis of cell cycle-related proteins in mediastinal lymph nodes of patients with N2-NSCLC obtained by EBUS-TBNA: relevance to chemotherapy response Thorax, July 1, 2008; 63(7): 642 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Salaun, R. Sesboue, S. Moreno-Swirc, J. Metayer, S. Bota, J. Bourguignon, and L. Thiberville Molecular Predictive Factors for Progression of High-Grade Preinvasive Bronchial Lesions Am. J. Respir. Crit. Care Med., April 15, 2008; 177(8): 880 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Roca, R. M. Kypta, and M. d. M. Vivanco Loss of p16INK4a results in increased glucocorticoid receptor activity during fibrosarcoma development PNAS, March 18, 2003; 100(6): 3113 - 3118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bai, X.-H. Pei, V. L. Godfrey, and Y. Xiong Haploinsufficiency of p18INK4c Sensitizes Mice to Carcinogen-Induced Tumorigenesis Mol. Cell. Biol., February 15, 2003; 23(4): 1269 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Nicholson, N. T. Okby, M. A. Khan, J. A. Welsh, M. G. McMenamin, W. D. Travis, J. R. Jett, H. D. Tazelaar, V. Trastek, P. C. Pairolero, et al. Alterations of p14ARF, p53, and p73 Genes Involved in the E2F-1-mediated Apoptotic Pathways in Non-Small Cell Lung Carcinoma Cancer Res., July 1, 2001; 61(14): 5636 - 5643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. I. Shapiro, J. G. Supko, A. Patterson, C. Lynch, J. Lucca, P. F. Zacarola, A. Muzikansky, J. J. Wright, T. J. Lynch Jr., and B. J. Rollins A Phase II Trial of the Cyclin-dependent Kinase Inhibitor Flavopiridol in Patients with Previously Untreated Stage IV Non-Small Cell Lung Cancer Clin. Cancer Res., June 1, 2001; 7(6): 1590 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Yu, R. G. Foster, and D. C. Dean Transcriptional Repression by Rb-E2F and Regulation of Anchorage-Independent Survival Mol. Cell. Biol., May 15, 2001; 21(10): 3325 - 3335. [Abstract] [Full Text]
|
|
|
|
|
|
D.-H. Kim, H. H. Nelson, J. K. Wiencke, S. Zheng, D. C. Christiani, J. C. Wain, E. J. Mark, and K. T. Kelsey p16INK4a and Histology-specific Methylation of CpG Islands by Exposure to Tobacco Smoke in Non-Small Cell Lung Cancer Cancer Res., April 1, 2001; 61(8): 3419 - 3424. [Abstract] [Full Text]
|
|
|
|
|
|
K. Suzuki, J. Fueyo, V. Krasnykh, P. N. Reynolds, D. T. Curiel, and R. Alemany A Conditionally Replicative Adenovirus with Enhanced Infectivity Shows Improved Oncolytic Potency Clin. Cancer Res., January 1, 2001; 7(1): 120 - 126. [Abstract] [Full Text]
|
|
|
|
|
|
M. Seike, A. Gemma, Y. Hosoya, S. Hemmi, Y. Taniguchi, Y. Fukuda, N. Yamanaka, and S. Kudoh Increase in the Frequency of p16INK4 Gene Inactivation by Hypermethylation in Lung Cancer during the Process of Metastasis and Its Relation to the Status of p53 Clin. Cancer Res., November 1, 2000; 6(11): 4307 - 4313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fuxe, G. Akusjärvi, H. M. Goike, G. Roos, V. P. Collins, and R. F. Pettersson Adenovirus-mediated Overexpression of p15INK4B Inhibits Human Glioma Cell Growth, Induces Replicative Senescence, and Inhibits Telomerase Activity Similarly to p16INK4A Cell Growth Differ., July 1, 2000; 11(7): 373 - 384. [Abstract] [Full Text]
|
|
|
|
|
|
W. N. ROM, J. G. HAY, T. C. LEE, Y. JIANG, and K.-M. TCHOU-WONG Molecular and Genetic Aspects of Lung Cancer Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1355 - 1367. [Full Text]
|
|
|
|
|
|
M. Omura-Minamisawa, M. B. Diccianni, A. Batova, R. C. Chang, L. J. Bridgeman, J. Yu, J. Pullen, W. P. Bowman, and A. L. Yu Universal Inactivation of Both p16 and p15 but not Downstream Components Is an Essential Event in the Pathogenesis of T-Cell Acute Lymphoblastic Leukemia Clin. Cancer Res., April 1, 2000; 6(4): 1219 - 1228. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. M. Fong, Y. Sekido, and J. D. Minna MOLECULAR PATHOGENESIS OF LUNG CANCER J. Thorac. Cardiovasc. Surg., December 1, 1999; 118(6): 1136 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Shapiro, D. A. Koestner, C. B. Matranga, and B. J. Rollins Flavopiridol Induces Cell Cycle Arrest and p53-independent Apoptosis in Non-Small Cell Lung Cancer Cell Lines Clin. Cancer Res., October 1, 1999; 5(10): 2925 - 2938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Mack, D. R. Gandara, C. Bowen, M. J. Edelman, T. Paglieroni, J. B. Schnier, E. P. Gelmann, and P. H. Gumerlock RB Status as a Determinant of Response to UCN-01 in Non-Small Cell Lung Carcinoma Clin. Cancer Res., September 1, 1999; 5(9): 2596 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kohno and J. Yokota1 How many tumor suppressor genes are involved in human lung carcinogenesis? Carcinogenesis, August 1, 1999; 20(8): 1403 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bissig, J. Richter, R. Desper, V. Meier, P. Schraml, A. A. Schaffer, G. Sauter, M. J. Mihatsch, and H. Moch Evaluation of the Clonal Relationship between Primary and Metastatic Renal Cell Carcinoma by Comparative Genomic Hybridization Am. J. Pathol., July 1, 1999; 155(1): 267 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Geradts, K. M. Fong, P. V. Zimmerman, R. Maynard, and J. D. Minna Correlation of Abnormal RB, p16ink4a, and p53 Expression with 3p Loss of Heterozygosity, Other Genetic Abnormalities, and Clinical Features in 103 Primary Non-Small Cell Lung Cancers Clin. Cancer Res., April 1, 1999; 5(4): 791 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Brambilla, S. Gazzeri, D. Moro, S. Lantuejoul, S. Veyrenc, and C. Brambilla Alterations of Rb Pathway (Rb-p16INK4-Cyclin D1) in Preinvasive Bronchial Lesions Clin. Cancer Res., February 1, 1999; 5(2): 243 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Xing, Y. Nie, L.-D. Wang, G.-Y. Yang, and C. S. Yang Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in human esophageal cancer in Linxian, China Carcinogenesis, January 1, 1999; 20(1): 77 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Gorgoulis, P. Zacharatos, A. Kotsinas, T. Liloglou, A. Kyroudi, M. Veslemes, A. Rassidakis, T. D. Halazonetis, J. K. Field, and C. Kittas Alterations of the p16-pRb Pathway and the Chromosome Locus 9p21–22 in Non-Small-Cell Lung Carcinomas : Relationship with p53 and MDM2 Protein Expression Am. J. Pathol., December 1, 1998; 153(6): 1749 - 1765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. DeMuth, C. M. Jackson, D. A. Weaver, E. L. Crawford, D. S. Durzinsky, S. J. Durham, A. Zaher, E. R. Phillips, S. A. Khuder, and J. C. Willey The Gene Expression Index c-myc × E2F-1/p21 Is Highly Predictive of Malignant Phenotype in Human Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., July 1, 1998; 19(1): 18 - 24. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Pinyol, F. Cobo, S. Bea, P. Jares, I. Nayach, P. L. Fernandez, E. Montserrat, A. Cardesa, and E. Campo p16INK4a Gene Inactivation by Deletions, Mutations, and Hypermethylation Is Associated With Transformed and Aggressive Variants of Non-Hodgkin's Lymphomas Blood, April 15, 1998; 91(8): 2977 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-W. Tchou, W. N. Rom, and K.-M. Tchou-Wong Novel Form of p21WAF1/CIP1/SDI1 Protein in Phorbol Ester-induced G2/M Arrest J. Biol. Chem., November 22, 1996; 271(47): 29556 - 29560. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
