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. 1998 Nov;78(10):1356–1360. doi: 10.1038/bjc.1998.684

Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.

P Jaïs 1, J C Sabourin 1, J Bombled 1, P Rougier 1, P Lasser 1, P Duvillard 1, J Bénard 1, B Bressac-de Paillerets 1
PMCID: PMC2063196  PMID: 9823979

Abstract

The human EB1 gene product was recently found, by a yeast two-hybrid screening, to be associated with the carboxy terminus of the APC (adenomatous polyposis coli) protein, the product of a tumour-suppressor gene thought to act as a gatekeeper in colorectal carcinogenesis. Because virtually all of the APC mutations result in the synthesis of carboxy-terminal truncated proteins, mutant APC proteins are expected to lose their ability to interact with EB1 gene product. Thus, the interaction between APC and EB1 proteins may be important for the tumour-suppressor activity of APC protein, and raises the hypothesis that EB1 is also involved in sporadic colorectal tumorigenesis. To investigate this hypothesis, somatic mutations in the entire coding sequence of EB1 cDNA were searched by reverse transcriptase single-strand conformational polymorphism (SSCP) analysis in 21 sporadic colorectal cancers and seven adenomas. None of these tumours contained somatic mutation, whereas a silent cDNA variant was identified in 14% of alleles. Furthermore, to investigate whether EB1 locus was included within a region subjected to losses of heterozygosity, four polymorphism markers surrounding EB1 locus were surveyed. Only one out of 28 colorectal tumours contained a loss of heterozygosity at the D20S107 marker. In conclusion, the present findings strongly suggest that EB1 gene is not involved in somatic colorectal carcinogenesis.

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Selected References

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  1. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  2. Chumakov I. M., Rigault P., Le Gall I., Bellanné-Chantelot C., Billault A., Guillou S., Soularue P., Guasconi G., Poullier E., Gros I. A YAC contig map of the human genome. Nature. 1995 Sep 28;377(6547 Suppl):175–297. doi: 10.1038/377175a0. [DOI] [PubMed] [Google Scholar]
  3. De Vries E. M., Ricke D. O., De Vries T. N., Hartmann A., Blaszyk H., Liao D., Soussi T., Kovach J. S., Sommer S. S. Database of mutations in the p53 and APC tumor suppressor genes designed to facilitate molecular epidemiological analyses. Hum Mutat. 1996;7(3):202–213. doi: 10.1002/(SICI)1098-1004(1996)7:3<202::AID-HUMU4>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  4. Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [PubMed] [Google Scholar]
  5. Hiltunen M. O., Alhonen L., Koistinaho J., Myöhänen S., Päkkönen M., Marin S., Kosma V. M., Jänne J. Hypermethylation of the APC (adenomatous polyposis coli) gene promoter region in human colorectal carcinoma. Int J Cancer. 1997 Mar 17;70(6):644–648. doi: 10.1002/(sici)1097-0215(19970317)70:6<644::aid-ijc3>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  6. Joslyn G., Richardson D. S., White R., Alber T. Dimer formation by an N-terminal coiled coil in the APC protein. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11109–11113. doi: 10.1073/pnas.90.23.11109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kane M. F., Loda M., Gaida G. M., Lipman J., Mishra R., Goldman H., Jessup J. M., Kolodner R. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997 Mar 1;57(5):808–811. [PubMed] [Google Scholar]
  8. Kinzler K. W., Nilbert M. C., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hamilton S. R., Hedge P., Markham A. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991 Mar 15;251(4999):1366–1370. doi: 10.1126/science.1848370. [DOI] [PubMed] [Google Scholar]
  9. Kinzler K. W., Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996 Oct 18;87(2):159–170. doi: 10.1016/s0092-8674(00)81333-1. [DOI] [PubMed] [Google Scholar]
  10. Lazar V., Grandjouan S., Bognel C., Couturier D., Rougier P., Bellet D., Bressac-de Paillerets B. Accumulation of multiple mutations in tumour suppressor genes during colorectal tumorigenesis in HNPCC patients. Hum Mol Genet. 1994 Dec;3(12):2257–2260. doi: 10.1093/hmg/3.12.2257. [DOI] [PubMed] [Google Scholar]
  11. Liu B., Parsons R., Papadopoulos N., Nicolaides N. C., Lynch H. T., Watson P., Jass J. R., Dunlop M., Wyllie A., Peltomäki P. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med. 1996 Feb;2(2):169–174. doi: 10.1038/nm0296-169. [DOI] [PubMed] [Google Scholar]
  12. Miyoshi Y., Nagase H., Ando H., Horii A., Ichii S., Nakatsuru S., Aoki T., Miki Y., Mori T., Nakamura Y. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet. 1992 Jul;1(4):229–233. doi: 10.1093/hmg/1.4.229. [DOI] [PubMed] [Google Scholar]
  13. Morin P. J., Vogelstein B., Kinzler K. W. Apoptosis and APC in colorectal tumorigenesis. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7950–7954. doi: 10.1073/pnas.93.15.7950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Muhua L., Adames N. R., Murphy M. D., Shields C. R., Cooper J. A. A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein. Nature. 1998 Jun 4;393(6684):487–491. doi: 10.1038/31014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Munemitsu S., Souza B., Müller O., Albert I., Rubinfeld B., Polakis P. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 1994 Jul 15;54(14):3676–3681. [PubMed] [Google Scholar]
  16. Nagase H., Nakamura Y. Mutations of the APC (adenomatous polyposis coli) gene. Hum Mutat. 1993;2(6):425–434. doi: 10.1002/humu.1380020602. [DOI] [PubMed] [Google Scholar]
  17. Pancer Z., Cooper E. L., Müller W. E. A urochordate putative homolog of human EB1, the protein which binds APC1. Cancer Lett. 1996 Dec 3;109(1-2):155–160. doi: 10.1016/s0304-3835(96)04440-0. [DOI] [PubMed] [Google Scholar]
  18. Renner C., Pfitzenmeier J. P., Gerlach K., Held G., Ohnesorge S., Sahin U., Bauer S., Pfreundschuh M. RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells. J Immunol. 1997 Aug 1;159(3):1276–1283. [PubMed] [Google Scholar]
  19. Rubinfeld B., Souza B., Albert I., Müller O., Chamberlain S. H., Masiarz F. R., Munemitsu S., Polakis P. Association of the APC gene product with beta-catenin. Science. 1993 Dec 10;262(5140):1731–1734. doi: 10.1126/science.8259518. [DOI] [PubMed] [Google Scholar]
  20. Schwartz K., Richards K., Botstein D. BIM1 encodes a microtubule-binding protein in yeast. Mol Biol Cell. 1997 Dec;8(12):2677–2691. doi: 10.1091/mbc.8.12.2677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shibata T., Gotoh M., Ochiai A., Hirohashi S. Association of plakoglobin with APC, a tumor suppressor gene product, and its regulation by tyrosine phosphorylation. Biochem Biophys Res Commun. 1994 Aug 30;203(1):519–522. doi: 10.1006/bbrc.1994.2213. [DOI] [PubMed] [Google Scholar]
  22. Smith K. J., Johnson K. A., Bryan T. M., Hill D. E., Markowitz S., Willson J. K., Paraskeva C., Petersen G. M., Hamilton S. R., Vogelstein B. The APC gene product in normal and tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846–2850. doi: 10.1073/pnas.90.7.2846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Su L. K., Burrell M., Hill D. E., Gyuris J., Brent R., Wiltshire R., Trent J., Vogelstein B., Kinzler K. W. APC binds to the novel protein EB1. Cancer Res. 1995 Jul 15;55(14):2972–2977. [PubMed] [Google Scholar]
  24. Su L. K., Vogelstein B., Kinzler K. W. Association of the APC tumor suppressor protein with catenins. Science. 1993 Dec 10;262(5140):1734–1737. doi: 10.1126/science.8259519. [DOI] [PubMed] [Google Scholar]
  25. Thorstensen L., Qvist H., Nesland J. M., Giercksky K. E., Lothe R. A. Allelotype profiles of local recurrences and distant metastases from colorectal-cancer patients. Int J Cancer. 1996 Dec 20;69(6):452–456. doi: 10.1002/(SICI)1097-0215(19961220)69:6<452::AID-IJC6>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
  26. Vasen H. F., Mecklin J. P., Khan P. M., Lynch H. T. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991 May;34(5):424–425. doi: 10.1007/BF02053699. [DOI] [PubMed] [Google Scholar]
  27. 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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