Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Jan;67(1):93–98. doi: 10.1038/bjc.1993.15

The TP53 tumour suppressor gene in colorectal carcinomas. II. Relation to DNA ploidy pattern and clinicopathological variables.

G I Meling 1, R A Lothe 1, A L Børresen 1, C Graue 1, S Hauge 1, O P Clausen 1, T O Rognum 1
PMCID: PMC1968222  PMID: 8427784

Abstract

Heterozygous loss of the TP53 gene on chromosome arm 17p in colorectal carcinomas was strongly associated with DNA aneuploidy (P < 0.0001). This association was seen only in tumours with loss on both 17p and 17q (P < 0.001), but not for loss on 17p only. DNA near diploid (ND) carcinomas and DNA aneuploid (AN) tumours with DNA index > or = 1.1 and < 1.3 had similar frequencies of TP53 gene loss (49% and 42%, respectively), whereas AN tumours with DNA index > or = 1.3 had a significantly higher frequency of TP53 gene loss (85%) (P < 0.0001 and P < 0.0001, respectively). There was a significant association between loss of the TP53 gene and histological grade (P < 0.01), and there tended to be an association between loss of the TP53 gene and degree of cellular atypia (P < 0.05), with TP53 gene loss being most frequent in moderately differentiated carcinomas, and in carcinomas with severe cellular atypia, respectively. The proportion of tumours with loss of the TP53 gene increased significantly towards the distal part of the large bowel (P < 0.0001). These results indicate that different genetic mechanisms may be involved in the carcinogenesis in colon and rectum carcinomas, and in the two subsets of DNA aneuploid carcinomas. Furthermore, the data may suggest a role for the TP53 gene in the aneuploidisation process, possibly as a 'target' for a whole chromosome loss.

Full text

PDF
93

Selected References

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

  1. Atkin N. B. Chromosome 1 aberrations in cancer. Cancer Genet Cytogenet. 1986 Apr 15;21(4):279–285. doi: 10.1016/0165-4608(86)90206-2. [DOI] [PubMed] [Google Scholar]
  2. Bufill J. A. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990 Nov 15;113(10):779–788. doi: 10.7326/0003-4819-113-10-779. [DOI] [PubMed] [Google Scholar]
  3. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  4. Couturier-Turpin M. H., Esnous C., Louvel A., Poirier Y., Couturier D. Chromosome 1 in human colorectal tumors. Cytogenetic research on structural changes and their significance. Hum Genet. 1992 Feb;88(4):431–438. doi: 10.1007/BF00215678. [DOI] [PubMed] [Google Scholar]
  5. Crissman H. A., Steinkamp J. A. Rapid, one step staining procedures for analysis of cellular DNA and protein by single and dual laser flow cytometry. Cytometry. 1982 Sep;3(2):84–90. doi: 10.1002/cyto.990030204. [DOI] [PubMed] [Google Scholar]
  6. Delattre O., Olschwang S., Law D. J., Melot T., Remvikos Y., Salmon R. J., Sastre X., Validire P., Feinberg A. P., Thomas G. Multiple genetic alterations in distal and proximal colorectal cancer. Lancet. 1989 Aug 12;2(8659):353–356. doi: 10.1016/s0140-6736(89)90537-0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Fisher E. R., Sass R., Palekar A., Fisher B., Wolmark N. Dukes' classification revisited. Findings from the National Surgical Adjuvant Breast and Bowel Projects (Protocol R-01). Cancer. 1989 Dec 1;64(11):2354–2360. doi: 10.1002/1097-0142(19891201)64:11<2354::aid-cncr2820641127>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  10. Frei J. V. Hereditary nonpolyposis colorectal cancer (Lynch syndrome II). Diploid malignancies with prolonged survival. Cancer. 1992 Mar 1;69(5):1108–1111. doi: 10.1002/cncr.2820690507. [DOI] [PubMed] [Google Scholar]
  11. Friend S. H., Dryja T. P., Weinberg R. A. Oncogenes and tumor-suppressing genes. N Engl J Med. 1988 Mar 10;318(10):618–622. doi: 10.1056/NEJM198803103181007. [DOI] [PubMed] [Google Scholar]
  12. Giaretti W., Santi L. Tumor progression by DNA flow cytometry in human colorectal cancer. Int J Cancer. 1990 Apr 15;45(4):597–603. doi: 10.1002/ijc.2910450404. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Høyheim B., Nakamura Y., White R. A BamHI-polymorphism is detected by a genomic p53-clone (pBHP53). Nucleic Acids Res. 1989 Nov 11;17(21):8898–8898. doi: 10.1093/nar/17.21.8898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kirkhus B., Clausen O. P., Fjordvang H., Helander K., Iversen O. H., Reitan J. B., Vaage S. Characterization of bladder tumours by multiparameter flow cytometry with special reference to grade II tumours. APMIS. 1988 Sep;96(9):783–792. doi: 10.1111/j.1699-0463.1988.tb00945.x. [DOI] [PubMed] [Google Scholar]
  16. Kouri M., Laasonen A., Mecklin J. P., Järvinen H., Franssila K., Pyrhönen S. Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry. Cancer. 1990 Apr 15;65(8):1825–1829. doi: 10.1002/1097-0142(19900415)65:8<1825::aid-cncr2820650827>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  17. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leister I., Weith A., Brüderlein S., Cziepluch C., Kangwanpong D., Schlag P., Schwab M. Human colorectal cancer: high frequency of deletions at chromosome 1p35. Cancer Res. 1990 Nov 15;50(22):7232–7235. [PubMed] [Google Scholar]
  19. Levine A. J., Momand J., Finlay C. A. The p53 tumour suppressor gene. Nature. 1991 Jun 6;351(6326):453–456. doi: 10.1038/351453a0. [DOI] [PubMed] [Google Scholar]
  20. Lynch H. T., Kimberling W., Albano W. A., Lynch J. F., Biscone K., Schuelke G. S., Sandberg A. A., Lipkin M., Deschner E. E., Mikol Y. B. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource. Cancer. 1985 Aug 15;56(4):934–938. doi: 10.1002/1097-0142(19850815)56:4<934::aid-cncr2820560439>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  21. Meling G. I., Lothe R. A., Børresen A. L., Hauge S., Graue C., Clausen O. P., Rognum T. O. Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis. Br J Cancer. 1991 Sep;64(3):475–480. doi: 10.1038/bjc.1991.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meling G. I., Rognum T. O., Clausen O. P., Chen Y., Lunde O. C., Schlichting E., Wiig J. N., Hognestad J., Bakka A., Havig O. Association between DNA ploidy pattern and cellular atypia in colorectal carcinomas. A new clinical application of DNA flow cytometric study? Cancer. 1991 Mar 15;67(6):1642–1649. doi: 10.1002/1097-0142(19910315)67:6<1642::aid-cncr2820670628>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  23. Myers R., 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 pRMU3 on chromosome 17q [D17S24]. Nucleic Acids Res. 1988 Jan 25;16(2):784–784. doi: 10.1093/nar/16.2.784. [DOI] [PMC free article] [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. Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665–669. doi: 10.1126/science.1651563. [DOI] [PubMed] [Google Scholar]
  27. Rognum T. O., Lund E., Meling G. I., Langmark F. Near diploid large bowel carcinomas have better five-year survival than aneuploid ones. Cancer. 1991 Sep 1;68(5):1077–1081. doi: 10.1002/1097-0142(19910901)68:5<1077::aid-cncr2820680528>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  28. Rognum T. O., Thorud E., Lund E. Survival of large bowel carcinoma patients with different DNA ploidy. Br J Cancer. 1987 Nov;56(5):633–636. doi: 10.1038/bjc.1987.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rognum T. O., Thrane P. S., Korsrud F. R., Brandtzaeg P. Epithelial tumor markers: special markers of glandular differentiation. Curr Top Pathol. 1987;77:133–153. doi: 10.1007/978-3-642-71356-9_6. [DOI] [PubMed] [Google Scholar]
  30. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  31. Turnbull R. B., Jr, Kyle K., Watson F. R., Spratt J. Cancer of the colon: the influence of the no-touch isolation technic on survival rates. Ann Surg. 1967 Sep;166(3):420–427. doi: 10.1097/00000658-196709000-00010. [DOI] [PMC free article] [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. Wolley R. C., Schreiber K., Koss L. G., Karas M., Sherman A. DNA distribution in human colon carcinomas and its relationship to clinical behavior. J Natl Cancer Inst. 1982 Jul;69(1):15–22. [PubMed] [Google Scholar]

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

RESOURCES