Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1998 Dec;51(12):901–909. doi: 10.1136/jcp.51.12.901

Progression from colorectal adenoma to carcinoma is associated with non-random chromosomal gains as detected by comparative genomic hybridisation.

G A Meijer 1, M A Hermsen 1, J P Baak 1, P J van Diest 1, S G Meuwissen 1, J A Beliën 1, J M Hoovers 1, H Joenje 1, P J Snijders 1, J M Walboomers 1
PMCID: PMC501025  PMID: 10070331

Abstract

AIMS: Chromosomal gains and losses were surveyed by comparative genomic hybridisation (CGH) in a series of colorectal adenomas and carcinomas, in search of high risk genomic changes involved in colorectal carcinogenesis. METHODS: Nine colorectal adenomas and 14 carcinomas were analysed by CGH, and DNA ploidy was assessed with both flow and image cytometry. RESULTS: In the nine adenomas analysed, an average of 6.6 (range 1 to 11) chromosomal aberrations were identified. In the 14 carcinomas an average of 11.9 (range 5 to 17) events were found per tumour. In the adenomas the number of gains and losses was in balance (3.6 v 3.0) while in carcinomas gains occurred more often than losses (8.2 v 3.7). Frequent gains involved 13q, 7p, 8q, and 20q, whereas losses most often occurred at 18q, 4q, and 8p. Gains of 13q, 8q, and 20q, and loss of 18q occurred more often in carcinomas than in adenomas (p = 0.005, p = 0.05, p = 0.05, and p = 0.02, respectively). Aneuploid tumours showed more gains than losses (mean 9.3 v 4.9, p = 0.02), in contrast to diploid tumours where gains and losses were nearly balanced (mean 3.1 v 4.1, p = 0.5). CONCLUSIONS: The most striking difference between chromosomal aberrations in colorectal adenomas and carcinomas, as detected by CGH, is an increased number of chromosomal gains that show a nonrandom distribution. Gains of 13q and also of 20q and 8q seem especially to be involved in the progression of adenomas to carcinomas, possibly owing to low level overexpression of oncogenes at these loci.

Full text

PDF
901

Images in this article

901Image
on p.901

Selected References

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

  1. Bardi G., Sukhikh T., Pandis N., Fenger C., Kronborg O., Heim S. Karyotypic characterization of colorectal adenocarcinomas. Genes Chromosomes Cancer. 1995 Feb;12(2):97–109. doi: 10.1002/gcc.2870120204. [DOI] [PubMed] [Google Scholar]
  2. Böcking A., Giroud F., Reith A. Consensus report of the ESACP task force on standardization of diagnostic DNA image cytometry. European Society for Analytical Cellular Pathology. Anal Cell Pathol. 1995 Jan;8(1):67–74. [PubMed] [Google Scholar]
  3. Di Vinci A., Infusini E., Peveri C., Risio M., Rossini F. P., Giaretti W. Deletions at chromosome 1p by fluorescence in situ hybridization are an early event in human colorectal tumorigenesis. Gastroenterology. 1996 Jul;111(1):102–107. doi: 10.1053/gast.1996.v111.pm8698188. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Fujiwara Y., Emi M., Ohata H., Kato Y., Nakajima T., Mori T., Nakamura Y. Evidence for the presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma. Cancer Res. 1993 Mar 1;53(5):1172–1174. [PubMed] [Google Scholar]
  6. Goh H. S., Jass J. R. DNA content and the adenoma-carcinoma sequence in the colorectum. J Clin Pathol. 1986 Apr;39(4):387–392. doi: 10.1136/jcp.39.4.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gope R., Christensen M. A., Thorson A., Lynch H. T., Smyrk T., Hodgson C., Wildrick D. M., Gope M. L., Boman B. M. Increased expression of the retinoblastoma gene in human colorectal carcinomas relative to normal colonic mucosa. J Natl Cancer Inst. 1990 Feb 21;82(4):310–314. doi: 10.1093/jnci/82.4.310. [DOI] [PubMed] [Google Scholar]
  8. Griffin C. A., Lazar S., Hamilton S. R., Giardiello F. M., Long P., Krush A. J., Booker S. V. Cytogenetic analysis of intestinal polyps in polyposis syndromes: comparison with sporadic colorectal adenomas. Cancer Genet Cytogenet. 1993 May;67(1):14–20. doi: 10.1016/0165-4608(93)90038-n. [DOI] [PubMed] [Google Scholar]
  9. Hanash S. M. A role for chromosome 1 in colorectal cancer. Gastroenterology. 1996 Jul;111(1):250–252. doi: 10.1053/gast.1996.v111.agast961110250. [DOI] [PubMed] [Google Scholar]
  10. Hedley D. W., Friedlander M. L., Taylor I. W., Rugg C. A., Musgrove E. A. Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem. 1983 Nov;31(11):1333–1335. doi: 10.1177/31.11.6619538. [DOI] [PubMed] [Google Scholar]
  11. Herbergs J., Hopman A. H., De Bruïne A. P., Ramaekers F. C., Arends J. W. In situ hybridization and flow cytometric analysis of colorectal tumours suggests two routes of tumourigenesis characterized by gain of chromosome 7 or loss of chromosomes 17 and 18. J Pathol. 1996 Jul;179(3):243–247. doi: 10.1002/(SICI)1096-9896(199607)179:3<243::AID-PATH588>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  12. Hermsen M. A., Joenje H., Arwert F., Welters M. J., Braakhuis B. J., Bagnay M., Westerveld A., Slater R. Centromeric breakage as a major cause of cytogenetic abnormalities in oral squamous cell carcinoma. Genes Chromosomes Cancer. 1996 Jan;15(1):1–9. doi: 10.1002/(SICI)1098-2264(199601)15:1<1::AID-GCC1>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  13. Hermsen M. A., Meijer G. A., Baak J. P., Joenje H., Walboomers J. J. Comparative genomic hybridization: a new tool in cancer pathology. Hum Pathol. 1996 Apr;27(4):342–349. doi: 10.1016/s0046-8177(96)90106-9. [DOI] [PubMed] [Google Scholar]
  14. Ilyas M., Tomlinson I. P. Genetic pathways in colorectal cancer. Histopathology. 1996 May;28(5):389–399. doi: 10.1046/j.1365-2559.1996.339381.x. [DOI] [PubMed] [Google Scholar]
  15. Joenje H., Mathew C., Gluckman E. Fanconi anaemia research: current status and prospects. Eur J Cancer. 1995;31A(2):268–272. doi: 10.1016/0959-8049(94)00485-n. [DOI] [PubMed] [Google Scholar]
  16. Kallioniemi A., Kallioniemi O. P., Piper J., Tanner M., Stokke T., Chen L., Smith H. S., Pinkel D., Gray J. W., Waldman F. M. Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2156–2160. doi: 10.1073/pnas.91.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kallioniemi A., Kallioniemi O. P., Sudar D., Rutovitz D., Gray J. W., Waldman F., Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992 Oct 30;258(5083):818–821. doi: 10.1126/science.1359641. [DOI] [PubMed] [Google Scholar]
  18. Kallioniemi O. P., Kallioniemi A., Piper J., Isola J., Waldman F. M., Gray J. W., Pinkel D. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer. 1994 Aug;10(4):231–243. doi: 10.1002/gcc.2870100403. [DOI] [PubMed] [Google Scholar]
  19. Kinzler K. W., Vogelstein B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature. 1997 Apr 24;386(6627):761–763. doi: 10.1038/386761a0. [DOI] [PubMed] [Google Scholar]
  20. Knudson A. G. Antioncogenes and human cancer. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10914–10921. doi: 10.1073/pnas.90.23.10914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Konishi F., Morson B. C. Pathology of colorectal adenomas: a colonoscopic survey. J Clin Pathol. 1982 Aug;35(8):830–841. doi: 10.1136/jcp.35.8.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lengauer C., Kinzler K. W., Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997 Apr 10;386(6625):623–627. doi: 10.1038/386623a0. [DOI] [PubMed] [Google Scholar]
  23. Longy M., Saura R., Dumas F., Leseve J. F., Taine L., Goussot J. F., Couzigou P. Chromosome analysis of adenomatous polyps of the colon: possible existence of two differently evolving cytogenetic groups. Cancer Genet Cytogenet. 1993 May;67(1):7–13. doi: 10.1016/0165-4608(93)90037-m. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Pippard E. C., Hall A. J., Barker D. J., Bridges B. A. Cancer in homozygotes and heterozygotes of ataxia-telangiectasia and xeroderma pigmentosum in Britain. Cancer Res. 1988 May 15;48(10):2929–2932. [PubMed] [Google Scholar]
  27. Ried T., Knutzen R., Steinbeck R., Blegen H., Schröck E., Heselmeyer K., du Manoir S., Auer G. Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors. Genes Chromosomes Cancer. 1996 Apr;15(4):234–245. doi: 10.1002/(SICI)1098-2264(199604)15:4<234::AID-GCC5>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  28. Savelieva E., Belair C. D., Newton M. A., DeVries S., Gray J. W., Waldman F., Reznikoff C. A. 20q gain associates with immortalization: 20q13.2 amplification correlates with genome instability in human papillomavirus 16 E7 transformed human uroepithelial cells. Oncogene. 1997 Feb 6;14(5):551–560. doi: 10.1038/sj.onc.1200868. [DOI] [PubMed] [Google Scholar]
  29. Schlegel J., Stumm G., Scherthan H., Bocker T., Zirngibl H., Rüschoff J., Hofstädter F. Comparative genomic in situ hybridization of colon carcinomas with replication error. Cancer Res. 1995 Dec 15;55(24):6002–6005. [PubMed] [Google Scholar]
  30. Tanner M. M., Tirkkonen M., Kallioniemi A., Collins C., Stokke T., Karhu R., Kowbel D., Shadravan F., Hintz M., Kuo W. L. Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes. Cancer Res. 1994 Aug 15;54(16):4257–4260. [PubMed] [Google Scholar]
  31. Yaremko M. L., Wasylyshyn M. L., Paulus K. L., Michelassi F., Westbrook C. A. Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal carcinomas. Genes Chromosomes Cancer. 1994 May;10(1):1–6. doi: 10.1002/gcc.2870100102. [DOI] [PubMed] [Google Scholar]
  32. de Meulemeester M., Vink A., Jakobs M., Hermsen M., Steenman M., Slater R., Dietrich A., Mannens M. The application of microwave denaturation in comparative genomic hybridization. Genet Anal. 1996 Nov;13(5):129–133. doi: 10.1016/s1050-3862(96)00162-3. [DOI] [PubMed] [Google Scholar]
  33. du Manoir S., Speicher M. R., Joos S., Schröck E., Popp S., Döhner H., Kovacs G., Robert-Nicoud M., Lichter P., Cremer T. Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization. Hum Genet. 1993 Feb;90(6):590–610. doi: 10.1007/BF00202476. [DOI] [PubMed] [Google Scholar]
  34. van der Bosch K., Becker I., Savelyeva L., Brüderlein S., Schlag P., Schwab M. Deletions in the short arm of chromosome 8 are present in up to 90% of human colorectal cancer cell lines. Genes Chromosomes Cancer. 1992 Jul;5(1):91–95. doi: 10.1002/gcc.2870050114. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES