Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Sep;78(5):612–615. doi: 10.1038/bjc.1998.549

Sequential loss of heterozygosity in the progression of squamous cell carcinoma of the lung.

C Endo 1, M Sagawa 1, M Sato 1, Y Chen 1, A Sakurada 1, H Aikawa 1, S Takahashi 1, K Usuda 1, Y Saito 1, S Fujimura 1
PMCID: PMC2063071  PMID: 9744500

Abstract

Radiographically occult bronchogenic squamous cell carcinomas are early lung cancers that localize mainly in the bronchial wall, and are thought to be a good model for investigating genetic alterations through lung cancer progression. In order to elucidate sequential genetic changes in lung cancers, we analysed the incidence of allelic losses on chromosome regions 2q33, 3p21, 5q21, 7q31, 9p21 and 17p13 for 40 cases of radiographically occult bronchogenic squamous-cell carcinomas and 40 cases of advanced lung cancers microdissected. In this study we used eight microsatellite dinucleotide polymorphic markers. Frequent loss of heterozygosity (LOH) was observed on 3p21 (53%), 5q21 (44%) and 17p13 (61%) in roentgenographically occult bronchogenic squamous cell carcinomas. 2q, 7q and 9p were lost less frequently in both roentgenographically occult bronchogenic squamous cell carcinomas and advanced lung cancers. These results suggest that several tumour-suppressor genes are associated with lung cancer progression and that genetic changes on 3p21, 5q21 and 17p13 are early events.

Full text

PDF
615

Images in this article

Selected References

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

  1. Chung G. T., Sundaresan V., Hasleton P., Rudd R., Taylor R., Rabbitts P. H. Sequential molecular genetic changes in lung cancer development. Oncogene. 1995 Dec 21;11(12):2591–2598. [PubMed] [Google Scholar]
  2. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  3. Hung J., Kishimoto Y., Sugio K., Virmani A., McIntire D. D., Minna J. D., Gazdar A. F. Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA. 1995 Feb 15;273(7):558–563. [PubMed] [Google Scholar]
  4. Ieda S., Watatani M., Yoshida T., Kuroda K., Inui H., Yasutomi M. Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas. Surg Today. 1996;26(4):230–235. doi: 10.1007/BF00311580. [DOI] [PubMed] [Google Scholar]
  5. Kohno T., Morishita K., Takano H., Shapiro D. N., Yokota J. Homozygous deletion at chromosome 2q33 in human small-cell lung carcinoma identified by arbitrarily primed PCR genomic fingerprinting. Oncogene. 1994 Jan;9(1):103–108. [PubMed] [Google Scholar]
  6. Kohno T., Otsuka T., Takano H., Yamamoto T., Hamaguchi M., Terada M., Yokota J. Identification of a novel phospholipase C family gene at chromosome 2q33 that is homozygously deleted in human small cell lung carcinoma. Hum Mol Genet. 1995 Apr;4(4):667–674. doi: 10.1093/hmg/4.4.667. [DOI] [PubMed] [Google Scholar]
  7. Kondo M., Suzuki H., Ueda R., Osada H., Takagi K., Takahashi T., Takahashi T. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene. 1995 Mar 16;10(6):1193–1198. [PubMed] [Google Scholar]
  8. Merlo A., Herman J. G., Mao L., Lee D. J., Gabrielson E., Burger P. C., Baylin S. B., Sidransky D. 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995 Jul;1(7):686–692. doi: 10.1038/nm0795-686. [DOI] [PubMed] [Google Scholar]
  9. Nagamoto N., Saito Y., Sato M., Sagawa M., Kanma K., Takahashi S., Usuda K., Endo C., Fujimura S., Nakada T. Clinicopathological analysis of 19 cases of isolated carcinoma in situ of the bronchus. Am J Surg Pathol. 1993 Dec;17(12):1234–1243. doi: 10.1097/00000478-199312000-00004. [DOI] [PubMed] [Google Scholar]
  10. Okamoto A., Hussain S. P., Hagiwara K., Spillare E. A., Rusin M. R., Demetrick D. J., Serrano M., Hannon G. J., Shiseki M., Zariwala M. Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer Res. 1995 Apr 1;55(7):1448–1451. [PubMed] [Google Scholar]
  11. Saito Y., Nagamoto N., Ota S., Sato M., Sagawa M., Kamma K., Takahashi S., Usuda K., Endo C., Imai T. Results of surgical treatment for roentgenographically occult bronchogenic squamous cell carcinoma. J Thorac Cardiovasc Surg. 1992 Aug;104(2):401–407. [PubMed] [Google Scholar]
  12. Shiseki M., Kohno T., Nishikawa R., Sameshima Y., Mizoguchi H., Yokota J. Frequent allelic losses on chromosomes 2q, 18q, and 22q in advanced non-small cell lung carcinoma. Cancer Res. 1994 Nov 1;54(21):5643–5648. [PubMed] [Google Scholar]
  13. Sozzi G., Miozzo M., Donghi R., Pilotti S., Cariani C. T., Pastorino U., Della Porta G., Pierotti M. A. Deletions of 17p and p53 mutations in preneoplastic lesions of the lung. Cancer Res. 1992 Nov 1;52(21):6079–6082. [PubMed] [Google Scholar]
  14. Sundaresan V., Ganly P., Hasleton P., Rudd R., Sinha G., Bleehen N. M., Rabbitts P. p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. Oncogene. 1992 Oct;7(10):1989–1997. [PubMed] [Google Scholar]
  15. Thiberville L., Bourguignon J., Metayer J., Bost F., Diarra-Mehrpour M., Bignon J., Lam S., Martin J. P., Nouvet G. Frequency and prognostic evaluation of 3p21-22 allelic losses in non-small-cell lung cancer. Int J Cancer. 1995 Dec 20;64(6):371–377. doi: 10.1002/ijc.2910640604. [DOI] [PubMed] [Google Scholar]
  16. Thiberville L., Payne P., Vielkinds J., LeRiche J., Horsman D., Nouvet G., Palcic B., Lam S. Evidence of cumulative gene losses with progression of premalignant epithelial lesions to carcinoma of the bronchus. Cancer Res. 1995 Nov 15;55(22):5133–5139. [PubMed] [Google Scholar]
  17. Tsuchiya E., Nakamura Y., Weng S. Y., Nakagawa K., Tsuchiya S., Sugano H., Kitagawa T. Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma. Cancer Res. 1992 May 1;52(9):2478–2481. [PubMed] [Google Scholar]
  18. Wei M. H., Latif F., Bader S., Kashuba V., Chen J. Y., Duh F. M., Sekido Y., Lee C. C., Geil L., Kuzmin I. Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG. Cancer Res. 1996 Apr 1;56(7):1487–1492. [PubMed] [Google Scholar]
  19. Zenklusen J. C., Thompson J. C., Klein-Szanto A. J., Conti C. J. Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene. Cancer Res. 1995 Mar 15;55(6):1347–1350. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES