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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Aug 17;83(6):750–755. doi: 10.1054/bjoc.2000.1366

Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma

A S-G Lee 1,4, Y-C Seo 1, A Chang 1, S Tohari 1, K-W Eu 2, F Seow-Choen 2, J O’D McGee 3
PMCID: PMC2363538  PMID: 10952779

Abstract

Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22–q23 in several types of tumours of diverse cell origin. Previous investigations of LOH at this chromosomal region in colorectal carcinoma have been contradictory in their findings, and have only included between 1–4 loci. In order to define any regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the highest frequencies of LOH at D11S1340 (41.0%), located between 105.13–111.97 Mb from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located approximately 113 Mb from the centromere. No statistically significant associations between LOH and age-of-presentation or Dukes’ stage were found. LOH was observed in colorectal tumours of all Dukes’ stages, including Dukes’ stages A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23 occurs in the early stages of colorectal carcinoma. These results confirm the presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in the carcinogenesis of colorectal carcinoma, and will facilitate future identification of candidate genes. © 2000 Cancer Research Campaign

Keywords: loss of heterozygosity (LOH), chromosome 11q, tumour suppressor genes, colorectal carcinoma

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Selected References

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  1. Baffa R., Negrini M., Mandes B., Rugge M., Ranzani G. N., Hirohashi S., Croce C. M. Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach. Cancer Res. 1996 Jan 15;56(2):268–272. [PubMed] [Google Scholar]
  2. Blake T. J., Shapiro M., Morse H. C., 3rd, Langdon W. Y. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. Oncogene. 1991 Apr;6(4):653–657. [PubMed] [Google Scholar]
  3. Carter S. L., Negrini M., Baffa R., Gillum D. R., Rosenberg A. L., Schwartz G. F., Croce C. M. Loss of heterozygosity at 11q22-q23 in breast cancer. Cancer Res. 1994 Dec 1;54(23):6270–6274. [PubMed] [Google Scholar]
  4. Cawkwell L., Bell S. M., Lewis F. A., Dixon M. F., Taylor G. R., Quirke P. Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology. Br J Cancer. 1993 Jun;67(6):1262–1267. doi: 10.1038/bjc.1993.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Connolly K. C., Gabra H., Millwater C. J., Taylor K. J., Rabiasz G. J., Watson J. E., Smyth J. F., Wyllie A. H., Jodrell D. I. Identification of a region of frequent loss of heterozygosity at 11q24 in colorectal cancer. Cancer Res. 1999 Jun 15;59(12):2806–2809. [PubMed] [Google Scholar]
  6. Davis M., Hitchcock A., Foulkes W. D., Campbell I. G. Refinement of two chromosome 11q regions of loss of heterozygosity in ovarian cancer. Cancer Res. 1996 Feb 15;56(4):741–744. [PubMed] [Google Scholar]
  7. Evans M. F., Koreth J., Bakkenist C. J., Herrington C. S., McGee J. O. Allelic deletion at 11q23.3-q25 is an early event in cervical neoplasia. Oncogene. 1998 May 14;16(19):2557–2564. doi: 10.1038/sj.onc.1202039. [DOI] [PubMed] [Google Scholar]
  8. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  9. Gabra H., Watson J. E., Taylor K. J., Mackay J., Leonard R. C., Steel C. M., Porteous D. J., Smyth J. F. Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis. Cancer Res. 1996 Mar 1;56(5):950–954. [PubMed] [Google Scholar]
  10. Gryfe R., Swallow C., Bapat B., Redston M., Gallinger S., Couture J. Molecular biology of colorectal cancer. Curr Probl Cancer. 1997 Sep-Oct;21(5):233–300. doi: 10.1016/s0147-0272(97)80003-7. [DOI] [PubMed] [Google Scholar]
  11. Gu Y., Alder H., Nakamura T., Schichman S. A., Prasad R., Canaani O., Saito H., Croce C. M., Canaani E. Sequence analysis of the breakpoint cluster region in the ALL-1 gene involved in acute leukemia. Cancer Res. 1994 May 1;54(9):2327–2330. [PubMed] [Google Scholar]
  12. Gustafson C. E., Young J., Leggett B., Searle J., Chenevix-Trench G. Loss of heterozygosity on the long arm of chromosome 11 in colorectal tumours. Br J Cancer. 1994 Sep;70(3):395–397. doi: 10.1038/bjc.1994.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hampton G. M., Penny L. A., Baergen R. N., Larson A., Brewer C., Liao S., Busby-Earle R. M., Williams A. W., Steel C. M., Bird C. C. Loss of heterozygosity in cervical carcinoma: subchromosomal localization of a putative tumor-suppressor gene to chromosome 11q22-q24. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6953–6957. doi: 10.1073/pnas.91.15.6953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herbst R. A., Larson A., Weiss J., Cavenee W. K., Hampton G. M., Arden K. C. A defined region of loss of heterozygosity at 11q23 in cutaneous malignant melanoma. Cancer Res. 1995 Jun 15;55(12):2494–2496. [PubMed] [Google Scholar]
  15. Hui A. B., Lo K. W., Leung S. F., Choi P. H., Fong Y., Lee J. C., Huang D. P. Loss of heterozygosity on the long arm of chromosome 11 in nasopharyngeal carcinoma. Cancer Res. 1996 Jul 15;56(14):3225–3229. [PubMed] [Google Scholar]
  16. Iselius L., Lindsten J., Aurias A., Fraccaro M., Bastard C., Bottelli A. M., Bui T. H., Caufin D., Dalprà L., Delendi N. The 11q;22q translocation: a collaborative study of 20 new cases and analysis of 110 families. Hum Genet. 1983;64(4):343–355. doi: 10.1007/BF00292366. [DOI] [PubMed] [Google Scholar]
  17. Keldysh P. L., Dragani T. A., Fleischman E. W., Konstantinova L. N., Perevoschikov A. G., Pierotti M. A., Della Porta G., Kopnin B. P. 11q deletions in human colorectal carcinomas: cytogenetics and restriction fragment length polymorphism analysis. Genes Chromosomes Cancer. 1993 Jan;6(1):45–50. doi: 10.1002/gcc.2870060109. [DOI] [PubMed] [Google Scholar]
  18. Konstantinova L. N., Fleischman E. W., Knisch V. I., Perevozchikov A. G., Kopnin B. P. Karyotype peculiarities of human colorectal adenocarcinomas. Hum Genet. 1991 Mar;86(5):491–496. doi: 10.1007/BF00194640. [DOI] [PubMed] [Google Scholar]
  19. Koreth J., Bakkenist C. J., McGee J. O. Allelic deletions at chromosome 11q22-q23.1 and 11q25-qterm are frequent in sporadic breast but not colorectal cancers. Oncogene. 1997 Jan 30;14(4):431–437. doi: 10.1038/sj.onc.1200847. [DOI] [PubMed] [Google Scholar]
  20. Lindblom A., Sandelin K., Iselius L., Dumanski J., White I., Nordenskjöld M., Larsson C. Predisposition for breast cancer in carriers of constitutional translocation 11q;22q. Am J Hum Genet. 1994 May;54(5):871–876. [PMC free article] [PubMed] [Google Scholar]
  21. Monaco C., Negrini M., Sozzi G., Veronese M. L., Vorechovsky I., Godwin A. K., Croce C. M. Molecular cloning and characterization of LOH11CR2A, a new gene within a refined minimal region of LOH at 11q23. Genomics. 1997 Dec 1;46(2):217–222. doi: 10.1006/geno.1997.5036. [DOI] [PubMed] [Google Scholar]
  22. Negrini M., Rasio D., Hampton G. M., Sabbioni S., Rattan S., Carter S. L., Rosenberg A. L., Schwartz G. F., Shiloh Y., Cavenee W. K. Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: identification of a new region at 11q23.3. Cancer Res. 1995 Jul 15;55(14):3003–3007. [PubMed] [Google Scholar]
  23. Rasio D., Negrini M., Manenti G., Dragani T. A., Croce C. M. Loss of heterozygosity at chromosome 11q in lung adenocarcinoma: identification of three independent regions. Cancer Res. 1995 Sep 15;55(18):3988–3991. [PubMed] [Google Scholar]
  24. Risio M., Reato G., di Celle P. F., Fizzotti M., Rossini F. P., Foà R. Microsatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer. Cancer Res. 1996 Dec 1;56(23):5470–5474. [PubMed] [Google Scholar]
  25. Robertson G., Coleman A., Lugo T. G. A malignant melanoma tumor suppressor on human chromosome 11. Cancer Res. 1996 Oct 1;56(19):4487–4492. [PubMed] [Google Scholar]
  26. Tomlinson I. P., Bodmer W. F. Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis. J Clin Pathol. 1996 May;49(5):386–390. doi: 10.1136/jcp.49.5.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tomlinson I. P., Gammack A. J., Stickland J. E., Mann G. J., MacKie R. M., Kefford R. F., McGee J. O. Loss of heterozygosity in malignant melanoma at loci on chromosome 11 and 17 implicated in the pathogenesis of other cancers. Genes Chromosomes Cancer. 1993 Jul;7(3):169–172. doi: 10.1002/gcc.2870070310. [DOI] [PubMed] [Google Scholar]
  28. Tomlinson I. P., Strickland J. E., Lee A. S., Bromley L., Evans M. F., Morton J., McGee J. O. Loss of heterozygosity on chromosome 11 q in breast cancer. J Clin Pathol. 1995 May;48(5):424–428. doi: 10.1136/jcp.48.5.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang S. S., Esplin E. D., Li J. L., Huang L., Gazdar A., Minna J., Evans G. A. Alterations of the PPP2R1B gene in human lung and colon cancer. Science. 1998 Oct 9;282(5387):284–287. doi: 10.1126/science.282.5387.284. [DOI] [PubMed] [Google Scholar]
  30. Wingo P. A., Ries L. A., Rosenberg H. M., Miller D. S., Edwards B. K. Cancer incidence and mortality, 1973-1995: a report card for the U.S. Cancer. 1998 Mar 15;82(6):1197–1207. doi: 10.1002/(sici)1097-0142(19980315)82:6<1197::aid-cncr26>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]

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