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. 1995 May;71(5):1070–1073. doi: 10.1038/bjc.1995.206

Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17 with evidence for a specific target region.

B Leggett 1, J Young 1, R Buttenshaw 1, L Thomas 1, B Young 1, G Chenevix-Trench 1, J Searle 1, M Ward 1
PMCID: PMC2033787  PMID: 7734302

Abstract

Allelic loss is a common mechanism of inactivation of tumour-suppressor genes in colorectal carcinomas. A number of known or putative tumour-suppressor genes including NF1, BRCA1, NME1, NME2 and prohibitin are present on the long arm of chromosome 17, and this region has not been extensively analysed in colorectal tumours. In this study 72 colorectal carcinomas were examined for allelic loss at eight loci on chromosome 17. Allelic loss was frequent both at the p53 locus, which is known to be important in colorectal carcinoma, and also telomeric to p53 on 17p. Allelic loss continued to be present in more than 50% of cases in the pericentromeric region and on proximal 17q to the marker LEW101 (D17S40) at 17q22-23. The most telomeric markers on 17q showed lower rates of allelic loss. Analysis of cases with partial deletions which did not include the p53 locus showed a common region of overlap of the deletions centred on D17S40. This suggests the target of allelic loss on 17q is a tumour-suppressor gene in this 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. Andersen L. B., Wallace M. R., Marchuk D. A., Tavakkol R., Mitchell A., Saulino A. M., Collins F. S. A highly polymorphic cDNA probe in the NF1 gene. Nucleic Acids Res. 1991 Jul 11;19(13):3754–3754. doi: 10.1093/nar/19.13.3754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Backer J. M., Mendola C. E., Kovesdi I., Fairhurst J. L., O'Hara B., Eddy R. L., Jr, Shows T. B., Mathew S., Murty V. V., Chaganti R. S. Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene. 1993 Feb;8(2):497–502. [PubMed] [Google Scholar]
  3. Baker S. J., Preisinger A. C., Jessup J. M., Paraskeva C., Markowitz S., Willson J. K., Hamilton S., Vogelstein B. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 1990 Dec 1;50(23):7717–7722. [PubMed] [Google Scholar]
  4. Bowcock A. M., Anderson L. A., Friedman L. S., Black D. M., Osborne-Lawrence S., Rowell S. E., Hall J. M., Solomon E., King M. C. THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21. Am J Hum Genet. 1993 Apr;52(4):718–722. [PMC free article] [PubMed] [Google Scholar]
  5. Chandrasekharappa S. C., Gross L. A., King S. E., Collins F. S. The human NME2 gene lies within 18kb of NME1 in chromosome 17. Genes Chromosomes Cancer. 1993 Apr;6(4):245–248. doi: 10.1002/gcc.2870060411. [DOI] [PubMed] [Google Scholar]
  6. Cohn K. H., Wang F. S., Desoto-LaPaix F., Solomon W. B., Patterson L. G., Arnold M. R., Weimar J., Feldman J. G., Levy A. T., Leone A. Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. Lancet. 1991 Sep 21;338(8769):722–724. doi: 10.1016/0140-6736(91)91444-y. [DOI] [PubMed] [Google Scholar]
  7. Coles C., Thompson A. M., Elder P. A., Cohen B. B., Mackenzie I. M., Cranston G., Chetty U., Mackay J., Macdonald M., Nakamura Y. Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. Lancet. 1990 Sep 29;336(8718):761–763. doi: 10.1016/0140-6736(90)93236-i. [DOI] [PubMed] [Google Scholar]
  8. Cornelis R. S., Devilee P., van Vliet M., Kuipers-Dijkshoorn N., Kersenmaeker A., Bardoel A., Khan P. M., Cornelisse C. J. Allele loss patterns on chromosome 17q in 109 breast carcinomas indicate at least two distinct target regions. Oncogene. 1993 Mar;8(3):781–785. [PubMed] [Google Scholar]
  9. Cropp C. S., Lidereau R., Campbell G., Champene M. H., Callahan R. Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7737–7741. doi: 10.1073/pnas.87.19.7737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eccles D. M., Russell S. E., Haites N. E., Atkinson R., Bell D. W., Gruber L., Hickey I., Kelly K., Kitchener H., Leonard R. Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group. Oncogene. 1992 Oct;7(10):2069–2072. [PubMed] [Google Scholar]
  11. Fearon E. R., Cho K. R., Nigro J. M., Kern S. E., Simons J. W., Ruppert J. M., Hamilton S. R., Preisinger A. C., Thomas G., Kinzler K. W. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. doi: 10.1126/science.2294591. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Futreal P. A., Söderkvist P., Marks J. R., Iglehart J. D., Cochran C., Barrett J. C., Wiseman R. W. Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite length polymorphisms. Cancer Res. 1992 May 1;52(9):2624–2627. [PubMed] [Google Scholar]
  14. Godwin A. K., Vanderveer L., Schultz D. C., Lynch H. T., Altomare D. A., Buetow K. H., Daly M., Getts L. A., Masny A., Rosenblum N. A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumors distal to BRCA1. Am J Hum Genet. 1994 Oct;55(4):666–677. [PMC free article] [PubMed] [Google Scholar]
  15. Jacobs I. J., Smith S. A., Wiseman R. W., Futreal P. A., Harrington T., Osborne R. J., Leech V., Molyneux A., Berchuck A., Ponder B. A. A deletion unit on chromosome 17q in epithelial ovarian tumors distal to the familial breast/ovarian cancer locus. Cancer Res. 1993 Mar 15;53(6):1218–1221. [PubMed] [Google Scholar]
  16. Jones M. H., Nakamura Y. Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism. Genes Chromosomes Cancer. 1992 Jul;5(1):89–90. doi: 10.1002/gcc.2870050113. [DOI] [PubMed] [Google Scholar]
  17. Kondoleon S., Vissing H., Luo X. Y., Magenis R. E., Kellogg J., Litt M. A hypervariable RFLP on chromosome 17p13 is defined by an arbitrary single copy probe p144-D6 [HGM9 No. D17S34]. Nucleic Acids Res. 1987 Dec 23;15(24):10605–10605. doi: 10.1093/nar/15.24.10605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kondoleon S., van Tuinen P., Ledbetter D. H., Vissing H., Litt M. An anonymous single-copy clone, pC63, from chromosome 17q23-qter identifies a frequent RFLP [HGM9 No. D17S21]. Nucleic Acids Res. 1987 Nov 11;15(21):9096–9096. doi: 10.1093/nar/15.21.9096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leone A., McBride O. W., Weston A., Wang M. G., Anglard P., Cropp C. S., Goepel J. R., Lidereau R., Callahan R., Linehan W. M. Somatic allelic deletion of nm23 in human cancer. Cancer Res. 1991 May 1;51(9):2490–2493. [PubMed] [Google Scholar]
  20. Li Y., Bollag G., Clark R., Stevens J., Conroy L., Fults D., Ward K., Friedman E., Samowitz W., Robertson M. Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell. 1992 Apr 17;69(2):275–281. doi: 10.1016/0092-8674(92)90408-5. [DOI] [PubMed] [Google Scholar]
  21. Lindblom A., Skoog L., Andersen T. I., Rotstein S., Nordenskjöld M., Larsson C. Four separate regions on chromosome 17 show loss of heterozygosity in familial breast carcinomas. Hum Genet. 1993 Mar;91(1):6–12. doi: 10.1007/BF00230213. [DOI] [PubMed] [Google Scholar]
  22. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Muleris M., Salmon R. J., Dutrillaux B. Cytogenetics of colorectal adenocarcinomas. Cancer Genet Cytogenet. 1990 Jun;46(2):143–156. doi: 10.1016/0165-4608(90)90100-o. [DOI] [PubMed] [Google Scholar]
  24. Nakamura Y., Ballard L., Leppert M., O'Connell P., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pYNZ22) on chromosome 17p [D17S30]. Nucleic Acids Res. 1988 Jun 24;16(12):5707–5707. doi: 10.1093/nar/16.12.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nakamura Y., Holm T., Gillilan S., Leppert M., O'Connell P., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pTHH59) on chromosome 17q [D17S4]. Nucleic Acids Res. 1988 Apr 25;16(8):3598–3598. doi: 10.1093/nar/16.8.3598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nakamura Y., Lathrop M., O'Connell P., Leppert M., Barker D., Wright E., Skolnick M., Kondoleon S., Litt M., Lalouel J. M. A mapped set of DNA markers for human chromosome 17. Genomics. 1988 May;2(4):302–309. doi: 10.1016/0888-7543(88)90018-3. [DOI] [PubMed] [Google Scholar]
  27. Newland R. C., Chapuis P. H., Smyth E. J. The prognostic value of substaging colorectal carcinoma. A prospective study of 1117 cases with standardized pathology. Cancer. 1987 Aug 15;60(4):852–857. doi: 10.1002/1097-0142(19870815)60:4<852::aid-cncr2820600422>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  28. Saito H., Inazawa J., Saito S., Kasumi F., Koi S., Sagae S., Kudo R., Saito J., Noda K., Nakamura Y. Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors. Cancer Res. 1993 Jul 15;53(14):3382–3385. [PubMed] [Google Scholar]
  29. Sato T., Saito H., Swensen J., Olifant A., Wood C., Danner D., Sakamoto T., Takita K., Kasumi F., Miki Y. The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer. Cancer Res. 1992 Mar 15;52(6):1643–1646. [PubMed] [Google Scholar]
  30. Solomon E., Voss R., Hall V., Bodmer W. F., Jass J. R., Jeffreys A. J., Lucibello F. C., Patel I., Rider S. H. Chromosome 5 allele loss in human colorectal carcinomas. Nature. 1987 Aug 13;328(6131):616–619. doi: 10.1038/328616a0. [DOI] [PubMed] [Google Scholar]
  31. Varesco L., Caligo M. A., Simi P., Black D. M., Nardini V., Casarino L., Rocchi M., Ferrara G., Solomon E., Bevilacqua G. The NM23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with BglII. Genes Chromosomes Cancer. 1992 Jan;4(1):84–88. doi: 10.1002/gcc.2870040113. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Wang L., Patel U., Ghosh L., Chen H. C., Banerjee S. Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res. 1993 Feb 15;53(4):717–720. [PubMed] [Google Scholar]
  35. Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
  36. Yagüe J., Juan M., Leone A., Romero M., Cardesa A., Vives J., Steeg P. S., Campo E. BglII and EcoRI polymorphism of the human nm23-H1 gene (NME1). Nucleic Acids Res. 1991 Dec 11;19(23):6663–6663. doi: 10.1093/nar/19.23.6663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Young J., Searle J., Stitz R., Cowen A., Ward M., Chenevix-French G. Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in colorectal tumors. Cancer Res. 1992 Jan 15;52(2):285–289. [PubMed] [Google Scholar]

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