Abstract
Activation of protooncogenes and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer (23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Furthermore, in 7 of these 8 squamous-cell carcinomas, loss of heterozygosity from chromosome 17 was accompanied by loss of DNA sequences from chromosome 11. The spectrum of allelic sequences lost from chromosome 11 was, however, similar in every type of carcinoma studied, and the data show two regions commonly deleted from chromosome 11 (11pter-p15.5 and 11p13-q13) that may have a role in the pathogenesis of all these types of non-small-cell bronchogenic carcinoma. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. These data included only 6 of 16 cases where loss of heterozygosity involved a chromosomal locus previously shown to be lost consistently in small-cell lung cancer (DNF15S2). Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amstad P., Reddel R. R., Pfeifer A., Malan-Shibley L., Mark G. E., 3rd, Harris C. C. Neoplastic transformation of a human bronchial epithelial cell line by a recombinant retrovirus encoding viral Harvey ras. Mol Carcinog. 1988;1(3):151–160. doi: 10.1002/mc.2940010303. [DOI] [PubMed] [Google Scholar]
- Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
- Brauch H., Johnson B., Hovis J., Yano T., Gazdar A., Pettengill O. S., Graziano S., Sorenson G. D., Poiesz B. J., Minna J. Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med. 1987 Oct 29;317(18):1109–1113. doi: 10.1056/NEJM198710293171803. [DOI] [PubMed] [Google Scholar]
- Dobrovic A., Houle B., Belouchi A., Bradley W. E. erbA-related sequence coding for DNA-binding hormone receptor localized to chromosome 3p21-3p25 and deleted in small cell lung carcinoma. Cancer Res. 1988 Feb 1;48(3):682–685. [PubMed] [Google Scholar]
- Dumanski J. P., Carlbom E., Collins V. P., Nordenskjöld M. Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9275–9279. doi: 10.1073/pnas.84.24.9275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon E. R., Feinberg A. P., Hamilton S. H., Vogelstein B. Loss of genes on the short arm of chromosome 11 in bladder cancer. 1985 Nov 28-Dec 4Nature. 318(6044):377–380. doi: 10.1038/318377a0. [DOI] [PubMed] [Google Scholar]
- Fearon E. R., Hamilton S. R., Vogelstein B. Clonal analysis of human colorectal tumors. Science. 1987 Oct 9;238(4824):193–197. doi: 10.1126/science.2889267. [DOI] [PubMed] [Google Scholar]
- Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
- Gusella J. F. DNA polymorphism and human disease. Annu Rev Biochem. 1986;55:831–854. doi: 10.1146/annurev.bi.55.070186.004151. [DOI] [PubMed] [Google Scholar]
- Hansen M. F., Cavenee W. K. Genetics of cancer predisposition. Cancer Res. 1987 Nov 1;47(21):5518–5527. [PubMed] [Google Scholar]
- Hansen M. F., Koufos A., Gallie B. L., Phillips R. A., Fodstad O., Brøgger A., Gedde-Dahl T., Cavenee W. K. Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6216–6220. doi: 10.1073/pnas.82.18.6216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harbour J. W., Lai S. L., Whang-Peng J., Gazdar A. F., Minna J. D., Kaye F. J. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science. 1988 Jul 15;241(4863):353–357. doi: 10.1126/science.2838909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson B. E., Sakaguchi A. Y., Gazdar A. F., Minna J. D., Burch D., Marshall A., Naylor S. L. Restriction fragment length polymorphism studies show consistent loss of chromosome 3p alleles in small cell lung cancer patients' tumors. J Clin Invest. 1988 Aug;82(2):502–507. doi: 10.1172/JCI113624. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knudson A. G., Jr Genetics of human cancer. Annu Rev Genet. 1986;20:231–251. doi: 10.1146/annurev.ge.20.120186.001311. [DOI] [PubMed] [Google Scholar]
- Kok K., Osinga J., Carritt B., Davis M. B., van der Hout A. H., van der Veen A. Y., Landsvater R. M., de Leij L. F., Berendsen H. H., Postmus P. E. Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature. 1987 Dec 10;330(6148):578–581. doi: 10.1038/330578a0. [DOI] [PubMed] [Google Scholar]
- Koufos A., Hansen M. F., Copeland N. G., Jenkins N. A., Lampkin B. C., Cavenee W. K. Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature. 1985 Jul 25;316(6026):330–334. doi: 10.1038/316330a0. [DOI] [PubMed] [Google Scholar]
- Kovacs G., Erlandsson R., Boldog F., Ingvarsson S., Müller-Brechlin R., Klein G., Sümegi J. Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1571–1575. doi: 10.1073/pnas.85.5.1571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larsson C., Skogseid B., Oberg K., Nakamura Y., Nordenskjöld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988 Mar 3;332(6159):85–87. doi: 10.1038/332085a0. [DOI] [PubMed] [Google Scholar]
- Lee W. H., Bookstein R., Hong F., Young L. J., Shew J. Y., Lee E. Y. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science. 1987 Mar 13;235(4794):1394–1399. doi: 10.1126/science.3823889. [DOI] [PubMed] [Google Scholar]
- Naylor S. L., Johnson B. E., Minna J. D., Sakaguchi A. Y. Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature. 1987 Oct 1;329(6138):451–454. doi: 10.1038/329451a0. [DOI] [PubMed] [Google Scholar]
- Okamoto M., Sasaki M., Sugio K., Sato C., Iwama T., Ikeuchi T., Tonomura A., Sasazuki T., Miyaki M. Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli. Nature. 1988 Jan 21;331(6153):273–277. doi: 10.1038/331273a0. [DOI] [PubMed] [Google Scholar]
- Reddel R. R., Ke Y., Kaighn M. E., Malan-Shibley L., Lechner J. F., Rhim J. S., Harris C. C. Human bronchial epithelial cells neoplastically transformed by v-Ki-ras: altered response to inducers of terminal squamous differentiation. Oncogene Res. 1988;3(4):401–408. [PubMed] [Google Scholar]
- Schroeder W. T., Chao L. Y., Dao D. D., Strong L. C., Pathak S., Riccardi V., Lewis W. H., Saunders G. F. Nonrandom loss of maternal chromosome 11 alleles in Wilms tumors. Am J Hum Genet. 1987 May;40(5):413–420. [PMC free article] [PubMed] [Google Scholar]
- Scrable H. J., Witte D. P., Lampkin B. C., Cavenee W. K. Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping. Nature. 1987 Oct 15;329(6140):645–647. doi: 10.1038/329645a0. [DOI] [PubMed] [Google Scholar]
- Seizinger B. R., Martuza R. L., Gusella J. F. Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature. 1986 Aug 14;322(6080):644–647. doi: 10.1038/322644a0. [DOI] [PubMed] [Google Scholar]
- Seizinger B. R., de la Monte S., Atkins L., Gusella J. F., Martuza R. L. Molecular genetic approach to human meningioma: loss of genes on chromosome 22. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5419–5423. doi: 10.1073/pnas.84.15.5419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiraishi M., Morinaga S., Noguchi M., Shimosato Y., Sekiya T. Loss of genes on the short arm of chromosome 11 in human lung carcinomas. Jpn J Cancer Res. 1987 Dec;78(12):1302–1308. [PubMed] [Google Scholar]
- Solomon E., Voss R., Hall V., Bodmer W. F., Jass J. R., Jeffreys A. J., Lucibello F. C., Patel I., Rider S. H. Chromosome 5 allele loss in human colorectal carcinomas. Nature. 1987 Aug 13;328(6131):616–619. doi: 10.1038/328616a0. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Turleau C., de Grouchy J., Dufier J. L., Phuc L. H., Schmelck P. H., Rappaport R., Nihoul-Fékété C., Diebold N. Aniridia, male pseudohermaphroditism, gonadoblastoma, mental retardation, and del 11p13. Hum Genet. 1981;57(3):300–306. [PubMed] [Google Scholar]
- Yokota J., Wada M., Shimosato Y., Terada M., Sugimura T. Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9252–9256. doi: 10.1073/pnas.84.24.9252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zbar B., Brauch H., Talmadge C., Linehan M. Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. 1987 Jun 25-Jul 1Nature. 327(6124):721–724. doi: 10.1038/327721a0. [DOI] [PubMed] [Google Scholar]
- Zech L., Bergh J., Nilsson K. Karyotypic characterization of established cell lines and short-term cultures of human lung cancers. Cancer Genet Cytogenet. 1985 Feb 15;15(3-4):335–347. doi: 10.1016/0165-4608(85)90178-5. [DOI] [PubMed] [Google Scholar]
- de Martinville B., Francke U. The c-Ha-ras1, insulin and beta-globin loci map outside the deletion associated with aniridia-Wilms' tumour. Nature. 1983 Oct 13;305(5935):641–643. doi: 10.1038/305641a0. [DOI] [PubMed] [Google Scholar]
- van Heyningen V., Boyd P. A., Seawright A., Fletcher J. M., Fantes J. A., Buckton K. E., Spowart G., Porteous D. J., Hill R. E., Newton M. S. Molecular analysis of chromosome 11 deletions in aniridia-Wilms tumor syndrome. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8592–8596. doi: 10.1073/pnas.82.24.8592. [DOI] [PMC free article] [PubMed] [Google Scholar]