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. 1987 Dec;84(24):9252–9256. doi: 10.1073/pnas.84.24.9252

Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung.

J Yokota 1, M Wada 1, Y Shimosato 1, M Terada 1, T Sugimura 1
PMCID: PMC299731  PMID: 2892196

Abstract

By a molecular genetic approach using polymorphic DNA markers that detect allelic deletion of specific chromosomal regions, we analyzed for possible loss of chromosomal heterozygosity in five different histological types of lung cancers obtained from 47 patients. In small-cell carcinomas, the incidence of allelic deletions at three different chromosomal loci was extremely high; loss of heterozygosity was detected on chromosomes 3p in 7 of 7 patients (100%), 13q in 10 of 11 patients (91%), and 17p in 5 of 5 patients (100%). The deletions at these loci in small-cell carcinomas were observed even in the tumors without any clinical evidence of metastasis. Furthermore, loss of heterozygosity on chromosomes 3p and 13q occurred prior to NMYC amplification and chromosome 11p deletion. Loss of heterozygosity on chromosome 3p was also detected with high frequency in adenocarcinomas [5 of 6 patients (83%)]. Heterozygosity of chromosomes 13q and 17p was lost in 10 of 31 patients (32%) and in 3 of 12 patients (25%), respectively, of lung cancers other than small-cell carcinomas. These results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small-cell carcinoma, and those on chromosome 3p may play an important role in the genesis of adenocarcinoma.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barker D., Schafer M., White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell. 1984 Jan;36(1):131–138. doi: 10.1016/0092-8674(84)90081-3. [DOI] [PubMed] [Google Scholar]
  2. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  3. Cavenee W. K., Hansen M. F., Nordenskjold M., Kock E., Maumenee I., Squire J. A., Phillips R. A., Gallie B. L. Genetic origin of mutations predisposing to retinoblastoma. Science. 1985 Apr 26;228(4698):501–503. doi: 10.1126/science.3983638. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Fearon E. R., Vogelstein B., Feinberg A. P. Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours. Nature. 1984 May 10;309(5964):176–178. doi: 10.1038/309176a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fung Y. K., Murphree A. L., T'Ang A., Qian J., Hinrichs S. H., Benedict W. F. Structural evidence for the authenticity of the human retinoblastoma gene. Science. 1987 Jun 26;236(4809):1657–1661. doi: 10.1126/science.2885916. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Koufos A., Hansen M. F., Lampkin B. C., Workman M. L., Copeland N. G., Jenkins N. A., Cavenee W. K. Loss of alleles at loci on human chromosome 11 during genesis of Wilms' tumour. Nature. 1984 May 10;309(5964):170–172. doi: 10.1038/309170a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983 Nov 10;306(5939):194–196. doi: 10.1038/306194a0. [DOI] [PubMed] [Google Scholar]
  13. Lundberg C., Skoog L., Cavenee W. K., Nordenskjöld M. Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2372–2376. doi: 10.1073/pnas.84.8.2372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morstyn G., Brown J., Novak U., Gardner J., Bishop J., Garson M. Heterogeneous cytogenetic abnormalities in small cell lung cancer cell lines. Cancer Res. 1987 Jun 15;47(12):3322–3327. [PubMed] [Google Scholar]
  15. Mukai S., Dryja T. P. Loss of alleles at polymorphic loci on chromosome 2 in uveal melanoma. Cancer Genet Cytogenet. 1986 May;22(1):45–53. doi: 10.1016/0165-4608(86)90136-6. [DOI] [PubMed] [Google Scholar]
  16. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  17. Naylor S. L., Sakaguchi A. Y., Shen L. P., Bell G. I., Rutter W. J., Shows T. B. Polymorphic human somatostatin gene is located on chromosome 3. Proc Natl Acad Sci U S A. 1983 May;80(9):2686–2689. doi: 10.1073/pnas.80.9.2686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Orkin S. H., Goldman D. S., Sallan S. E. Development of homozygosity for chromosome 11p markers in Wilms' tumour. Nature. 1984 May 10;309(5964):172–174. doi: 10.1038/309172a0. [DOI] [PubMed] [Google Scholar]
  19. Reeve A. E., Housiaux P. J., Gardner R. J., Chewings W. E., Grindley R. M., Millow L. J. Loss of a Harvey ras allele in sporadic Wilms' tumour. Nature. 1984 May 10;309(5964):174–176. doi: 10.1038/309174a0. [DOI] [PubMed] [Google Scholar]
  20. Sakamoto H., Mori M., Taira M., Yoshida T., Matsukawa S., Shimizu K., Sekiguchi M., Terada M., Sugimura T. Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3997–4001. doi: 10.1073/pnas.83.11.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Whang-Peng J., Bunn P. A., Jr, Kao-Shan C. S., Lee E. C., Carney D. N., Gazdar A., Minna J. D. A nonrandom chromosomal abnormality, del 3p(14-23), in human small cell lung cancer (SCLC). Cancer Genet Cytogenet. 1982 Jun;6(2):119–134. doi: 10.1016/0165-4608(82)90077-2. [DOI] [PubMed] [Google Scholar]
  23. Whang-Peng J., Kao-Shan C. S., Lee E. C., Bunn P. A., Carney D. N., Gazdar A. F., Minna J. D. Specific chromosome defect associated with human small-cell lung cancer; deletion 3p(14-23). Science. 1982 Jan 8;215(4529):181–182. doi: 10.1126/science.6274023. [DOI] [PubMed] [Google Scholar]
  24. Yokota J., Tsunetsugu-Yokota Y., Battifora H., Le Fevre C., Cline M. J. Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation. Science. 1986 Jan 17;231(4735):261–265. doi: 10.1126/science.3941898. [DOI] [PubMed] [Google Scholar]
  25. 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]

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