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. 1998 Nov;78(9):1152–1155. doi: 10.1038/bjc.1998.645

Somatic alterations of the SMAD-2 gene in human colorectal cancers.

Y Takagi 1, H Koumura 1, M Futamura 1, S Aoki 1, K Ymaguchi 1, H Kida 1, H Tanemura 1, K Shimokawa 1, S Saji 1
PMCID: PMC2063002  PMID: 9820171

Abstract

The SMAD-2 gene, which is located at 18q21, has been identified as a candidate tumour-suppressor gene from work on colorectal cancers. The aim of the present study was to determine the clinical alterations and the significance of its mutations in a series of colorectal cancers previously examined for SMAD-4/DPC-4 gene. Mutation analyses of the SMAD-2 gene were carried out on cDNA samples from 36 primary colorectal cancer specimens using a combination of the polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing. Only one missense mutation (2.8%), producing an amino acid substitution in the highly conserved region, and two homozygous deletions (5.5%) of the total coding region of the SMAD-2 gene were detected in the 36 cancers. The SMAD-2 gene may play a role as a candidate tumour-suppressor gene in a small fraction of colorectal cancers. However, allelic loss at 18q21 is very often seen in this type of tumour. Even in combination with changes in SMAD-4, the observed frequency was not sufficient to account for all 18q21 deletions in colorectal cancers. Thus, another tumour-suppressor gene, such as DCC, discovered as the first tumour-suppressor candidate in the region may also exist in this chromosome region.

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Selected References

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

  1. Baylin S. B., Makos M., Wu J. J., Yen R. W., de Bustros A., Vertino P., Nelkin B. D. Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells. 1991 Oct;3(10):383–390. [PubMed] [Google Scholar]
  2. Brewster S. F., Gingell J. C., Browne S., Brown K. W. Loss of heterozygosity on chromosome 18q is associated with muscle-invasive transitional cell carcinoma of the bladder. Br J Cancer. 1994 Oct;70(4):697–700. doi: 10.1038/bjc.1994.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cliby W., Ritland S., Hartmann L., Dodson M., Halling K. C., Keeney G., Podratz K. C., Jenkins R. B. Human epithelial ovarian cancer allelotype. Cancer Res. 1993 May 15;53(10 Suppl):2393–2398. [PubMed] [Google Scholar]
  4. Eppert K., Scherer S. W., Ozcelik H., Pirone R., Hoodless P., Kim H., Tsui L. C., Bapat B., Gallinger S., Andrulis I. L. MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell. 1996 Aug 23;86(4):543–552. doi: 10.1016/s0092-8674(00)80128-2. [DOI] [PubMed] [Google Scholar]
  5. Fynan T. M., Reiss M. Resistance to inhibition of cell growth by transforming growth factor-beta and its role in oncogenesis. Crit Rev Oncog. 1993;4(5):493–540. [PubMed] [Google Scholar]
  6. Graff J. M., Bansal A., Melton D. A. Xenopus Mad proteins transduce distinct subsets of signals for the TGF beta superfamily. Cell. 1996 May 17;85(4):479–487. doi: 10.1016/s0092-8674(00)81249-0. [DOI] [PubMed] [Google Scholar]
  7. Hahn S. A., Schutte M., Hoque A. T., Moskaluk C. A., da Costa L. T., Rozenblum E., Weinstein C. L., Fischer A., Yeo C. J., Hruban R. H. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996 Jan 19;271(5247):350–353. doi: 10.1126/science.271.5247.350. [DOI] [PubMed] [Google Scholar]
  8. Hoodless P. A., Haerry T., Abdollah S., Stapleton M., O'Connor M. B., Attisano L., Wrana J. L. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell. 1996 May 17;85(4):489–500. doi: 10.1016/s0092-8674(00)81250-7. [DOI] [PubMed] [Google Scholar]
  9. Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
  10. Orita M., Iwahana H., Kanazawa H., Hayashi K., Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766–2770. doi: 10.1073/pnas.86.8.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Riggins G. J., Thiagalingam S., Rozenblum E., Weinstein C. L., Kern S. E., Hamilton S. R., Willson J. K., Markowitz S. D., Kinzler K. W., Vogelstein B. Mad-related genes in the human. Nat Genet. 1996 Jul;13(3):347–349. doi: 10.1038/ng0796-347. [DOI] [PubMed] [Google Scholar]
  12. Savage C., Das P., Finelli A. L., Townsend S. R., Sun C. Y., Baird S. E., Padgett R. W. Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):790–794. doi: 10.1073/pnas.93.2.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sekelsky J. J., Newfeld S. J., Raftery L. A., Chartoff E. H., Gelbart W. M. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics. 1995 Mar;139(3):1347–1358. doi: 10.1093/genetics/139.3.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shibagaki I., Shimada Y., Wagata T., Ikenaga M., Imamura M., Ishizaki K. Allelotype analysis of esophageal squamous cell carcinoma. Cancer Res. 1994 Jun 1;54(11):2996–3000. [PubMed] [Google Scholar]
  15. Suzuki H., Takahashi T., Kuroishi T., Suyama M., Ariyoshi Y., Takahashi T., Ueda R. p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. Cancer Res. 1992 Feb 1;52(3):734–736. [PubMed] [Google Scholar]
  16. Takagi Y., Kohmura H., Futamura M., Kida H., Tanemura H., Shimokawa K., Saji S. Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. Gastroenterology. 1996 Nov;111(5):1369–1372. doi: 10.1053/gast.1996.v111.pm8898652. [DOI] [PubMed] [Google Scholar]
  17. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  18. Vogelstein B., Fearon E. R., Kern S. E., Hamilton S. R., Preisinger A. C., Nakamura Y., White R. Allelotype of colorectal carcinomas. Science. 1989 Apr 14;244(4901):207–211. doi: 10.1126/science.2565047. [DOI] [PubMed] [Google Scholar]

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