| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
National Cancer Institute, Bethesda, Maryland 20892 [L. B., M. A. K., A. N. F., A. G., W. P. B., N. E. C., L. A. L., C. C. H.]; Institute of Oncology, 44-100 Gliwice, Poland [M. R.]; University of Utah Medical Center, Salt Lake City, Utah 84148 [D. G. G.]; Armed Forces Institute of Pathology, Washington, DC 20306 [M. V. F., W. D. T.]; Mayo Clinic Scottsdale, Scottsdale, Arizona 85259 [T. V. C.]; Mayo Clinic, Rochester, Minnesota 55905 [V. T., P. C. P., H. D. T., D. E. M.]
The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors plus recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38% at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (P = 0.03). We found that 63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26% with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis.
1 To whom requests for reprints should be addressed, at Laboratory of Human Carcinogenesis, National Cancer Institute, Building 37, Room 2C05, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255. Phone: (301) 496-2048; Fax: (301) 496-0497; E-mail: Curtis_Harris@nih.gov.
Received 3/12/98. Accepted 4/30/98.
This article has been cited by other articles:
|
|
 |
|
  R. Li, N. W. Todd, Q. Qiu, T. Fan, R. Y. Zhao, W. H. Rodgers, H.-B. Fang, R. L. Katz, S. A. Stass, and F. Jiang Genetic Deletions in Sputum as Diagnostic Markers for Early Detection of Stage I Non-Small Cell Lung Cancer Clin. Cancer Res., January 15, 2007; 13(2): 482 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bavi, Z. Jehan, V. Atizado, H. Al-Dossari, F. Al-Dayel, A. Tulbah, S. S. Amr, S. S. Sheikh, A. Ezzat, H. El-Solh, et al. Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis. Cancer Epidemiol. Biomarkers Prev., September 1, 2006; 15(9): 1708 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Semba and K. Huebner Protein Expression Profiling Identifies Cyclophilin A as a Molecular Target in Fhit-Mediated Tumor Suppression Mol. Cancer Res., August 1, 2006; 4(8): 529 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Kim, J. W. Kim, J. Han, Y. M. Shim, J. Park, and D.-H. Kim Cohypermethylation of p16 and FHIT Promoters as a Prognostic Factor of Recurrence in Surgically Resected Stage I Non-Small Cell Lung Cancer. Cancer Res., April 15, 2006; 66(8): 4049 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Burke, D. B. Flieder, D. G. Guinee, E. Brambilla, A. N. Freedman, W. P. Bennett, R. T. Jones, A. Borkowski, N. A. Caporaso, M. Fleming, et al. Prognostic Implications of Molecular and Immunohistochemical Profiles of the Rb and p53 Cell Cycle Regulatory Pathways in Primary Non-Small Cell Lung Carcinoma Clin. Cancer Res., January 1, 2005; 11(1): 232 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Kim, H. Kim, Y. M. Shim, J. Han, J. Park, and D.-H. Kim Aberrant methylation of the FHIT gene in chronic smokers with early stage squamous cell carcinoma of the lung Carcinogenesis, November 1, 2004; 25(11): 2165 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Yoshino, S. Fukuyama, T. Kameyama, Y. Shikada, S. Oda, Y. Maehara, and K. Sugimachi Detection of Loss of Heterozygosity by High-Resolution Fluorescent System in Non-small Cell Lung Cancer: Association of Loss of Heterozygosity With Smoking and Tumor Progression Chest, February 1, 2003; 123(2): 545 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sasatomi, S. D. Finkelstein, J. D. Woods, A. Bakker, P. A. Swalsky, J. D. Luketich, H. C. Fernando, and S. A. Yousem Comparison of Accumulated Allele Loss between Primary Tumor and Lymph Node Metastasis in Stage II Non-small Cell Lung Carcinoma: Implications for the Timing of Lymph Node Metastasis and Prognostic Value Cancer Res., May 1, 2002; 62(9): 2681 - 2689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Uematsu, A. Yoshimura, A. Gemma, H. Mochimaru, Y. Hosoya, S. Kunugi, K. Matsuda, M. Seike, F. Kurimoto, K. Takenaka, et al. Aberrations in the Fragile Histidine Triad (FHIT) Gene in Idiopathic Pulmonary Fibrosis Cancer Res., December 1, 2001; 61(23): 8527 - 8533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ishii, K. R. Dumon, A. Vecchione, L. Y. Y. Fong, R. Baffa, K. Huebner, and C. M. Croce Potential Cancer Therapy With the Fragile Histidine Triad Gene: Review of the Preclinical Studies JAMA, November 21, 2001; 286(19): 2441 - 2449. [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]
|
|
|
|
|
|
T. C. Krivak, J. W. McBroom, J. Seidman, D. Venzon, B. Crothers, P. J. MacKoul, G. S. Rose, J. W. Carlson, and M. J. Birrer Abnormal Fragile Histidine Triad (FHIT) Expression in Advanced Cervical Carcinoma: A Poor Prognostic Factor Cancer Res., June 1, 2001; 61(11): 4382 - 4385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hirao, H. H. Nelson, T. D. S. Ashok, J. C. Wain, E. J. Mark, D. C. Christiani, J. K. Wiencke, and K. T. Kelsey Tobacco Smoke-induced DNA Damage and an Early Age of Smoking Initiation Induce Chromosome Loss at 3p21 in Lung Cancer Cancer Res., January 1, 2001; 61(2): 612 - 615. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
J. W. Gray and C. Collins Genome changes and gene expression in human solid tumors Carcinogenesis, March 1, 2000; 21(3): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhou, B. L. Kemp, F. R. Khuri, D. Liu, J. J. Lee, W. Wu, W. K. Hong, and L. Mao Prognostic Implication of Microsatellite Alteration Profiles in Early-Stage Non-small Cell Lung Cancer Clin. Cancer Res., February 1, 2000; 6(2): 559 - 565. [Abstract] [Full Text]
|
|
|
|
|
|
X. P. Hao, J. E. Willis, T. G. Pretlow, J. S. Rao, G. T. MacLennan, I. C. Talbot, and T. P. Pretlow Loss of Fragile Histidine Triad Expression in Colorectal Carcinomas and Premalignant Lesions Cancer Res., January 1, 2000; 60(1): 18 - 21. [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]
|
|
|
|
|
|
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]
|
|
| 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 |
