This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herzog, C. R. Articles by You, M. Search for Related Content PubMed PubMed Citation Articles by Herzog, C. R. Articles by You, M.

Deletion Mapping of a Putative Tumor Suppressor Gene on Chromosome 4 in Mouse Lung Tumors¹

Department of Pathology, Medical College of Ohio, Toledo, Ohio 43699 [C. R. H., M. Y.], and National Institute for Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [R. W. W.]

Genetic and molecular studies have implicated the region of the -interferon gene cluster on mouse chromosome 4 as the location of a putative tumor suppressor gene. A region of homology on human chromosome 9p21–22 that is frequently deleted in multiple human cancers has recently been found to contain a candidate tumor suppressor gene called multiple tumor suppressor-1 (MTS1), which was previously shown to encode an inhibitor of cyclin-dependent kinase 4. We performed loss of heterozygosity and deletion analyses to map the most commonly deleted region on chromosome 4 in F₁ hybrid mouse lung tumors. Ten simple sequence length polymorphism markers were analyzed with focus on the -interferon region. Allelic losses were detected in 29 of 61 (48%) of the lung adenocarcinomas but in only 1 of 38 (3%) of the lung adenomas examined. In most cases, the losses appeared to occur by nondisjunction. However, in three carcinomas, we detected homozygous deletions that overlapped at simple sequence length polymorphism marker D4MIT77. These data suggest a critical region of about 2 cM immediately distal to the -interferon locus as the likely domain of a novel tumor suppressor gene on mouse chromosome 4, the loss of which appears to be involved in the progression of mouse lung tumorigenesis.

¹ This work was supported by NIH Grant CA58554.

² To whom requests for reprints should be addressed, at Department of Pathology, Medical College of Ohio, 3000 Arlington Ave., Toledo, OH 43699.

Received 5/27/94. Accepted 6/16/94.

This article has been cited by other articles:

				A. S. Tam, T. R. Devereux, A. C. Patel, J. F. Foley, R. R. Maronpot, and T. E. Massey Perturbations of the Ink4a/Arf gene locus in aflatoxin B1-induced mouse lung tumors Carcinogenesis, January 1, 2003; 24(1): 121 - 132. [Abstract] [Full Text] [PDF]

				C. R. Herzog, T. R. Devereux, B. Pittman, and M. You Carcinogenic Induction Directs the Selection of Allelic Losses in Mouse Lung Tumorigenesis Cancer Res., November 15, 2002; 62(22): 6424 - 6429. [Abstract] [Full Text] [PDF]

				L. M. Sargent, J. R. Senft, D. T. Lowry, A. M. Jefferson, F. L. Tyson, A. M. Malkinson, A. E. Coleman, and S. H. Reynolds Specific Chromosomal Aberrations in Mouse Lung Adenocarcinoma Cell Lines Detected by Spectral Karyotyping: A Comparison with Human Lung Adenocarcinoma Cancer Res., February 1, 2002; 62(4): 1152 - 1157. [Abstract] [Full Text] [PDF]

				A. C. Patel, C. H. Anna, J. F. Foley, P. S. Stockton, F. L. Tyson, J.C. Barrett, and T. R. Devereux Hypermethylation of the p16 Ink4a promoter in B6C3F1 mouse primary lung adenocarcinomas and mouse lung cell lines Carcinogenesis, September 1, 2000; 21(9): 1691 - 1700. [Abstract] [Full Text] [PDF]

				L. E. Lantry, Z. Zhang, R. Yao, K. A. Crist, Y. Wang, J. Ohkanda, A. D. Hamilton, S. M. Sebti, R. A. Lubet, and M. You Effect of farnesyltransferase inhibitor FTI-276 on established lung adenomas from A/J mice induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Carcinogenesis, January 1, 2000; 21(1): 113 - 116. [Abstract] [Full Text] [PDF]

				M. Cool and P. Jolicoeur Elevated Frequency of Loss of Heterozygosity in Mammary Tumors Arising in Mouse Mammary Tumor Virus/neu Transgenic Mice Cancer Res., May 1, 1999; 59(10): 2438 - 2444. [Abstract] [Full Text] [PDF]

				L. E. Lantry, Z. Zhang, K. A. Crist, Y. Wang, G. J. Kelloff, R. A. Lubet, and M. You 5-Aza-2'-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone-induced primary mouse lung tumor model Carcinogenesis, February 1, 1999; 20(2): 343 - 346. [Abstract] [Full Text] [PDF]

				E. H. Radany, K. Hong, S. Kesharvarzi, E. S. Lander, and J. M. Bishop Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4 PNAS, August 5, 1997; 94(16): 8664 - 8669. [Abstract] [Full Text] [PDF]

				B. F. Trump Mechanisms of Toxicity and Carcinogenesis Toxicol Pathol, November 1, 1995; 23(6): 775 - 827. [PDF]