Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes
Jean-Christophe Weber
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorNicolas Meyer
Département de Santé Publique, Hôpital Civil, Place de l'Hôpital, Strasbourg Cedex, France
Search for more papers by this authorErwan Pencreach
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorAnne Schneider
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorEric Guérin
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorAgnès Neuville
Laboratoire d'Anatomie Pathologique, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorChristine Stemmer
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorCécile Brigand
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorPhilippe Bachellier
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorSerge Rohr
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorMichèle Kedinger
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorChristian Meyer
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorDominique Guenot
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorPierre Oudet
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorDaniel Jaeck
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorCorresponding Author
Marie-Pierre Gaub
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Fax: +33-3-88-12-75-39.
Laboratoire de Biochimie et Biologie Moléculaire, INSERM U 682, Avenue Molière, 67098 Strasbourg Cedex, FranceSearch for more papers by this authorJean-Christophe Weber
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorNicolas Meyer
Département de Santé Publique, Hôpital Civil, Place de l'Hôpital, Strasbourg Cedex, France
Search for more papers by this authorErwan Pencreach
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorAnne Schneider
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorEric Guérin
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorAgnès Neuville
Laboratoire d'Anatomie Pathologique, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorChristine Stemmer
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorCécile Brigand
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorPhilippe Bachellier
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorSerge Rohr
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorMichèle Kedinger
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorChristian Meyer
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorDominique Guenot
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorPierre Oudet
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorDaniel Jaeck
Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Search for more papers by this authorCorresponding Author
Marie-Pierre Gaub
Laboratoire de Biochimie et Biologie Moléculaire, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
INSERM U682, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France
Fax: +33-3-88-12-75-39.
Laboratoire de Biochimie et Biologie Moléculaire, INSERM U 682, Avenue Molière, 67098 Strasbourg Cedex, FranceSearch for more papers by this authorAbstract
In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2-way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN-High, CIN-Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K-Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN-Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development. © 2006 Wiley-Liss, Inc.
References
- 1 Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759–67.
- 2 Ookawa K, Sakamoto M, Hirohashi S, Yoshida Y, Sugimura T, Terada M, Yokota J. Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma. Int J Cancer 1993; 53: 382–7.
- 3 Bardi G, Parada LA, Bomme L, Pandis N, Willen R, Johansson B, Jeppsson B, Beroukas K, Heim S, Mitelman F. Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer. Br J Cancer 1997; 76: 765–9.
- 4 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57–70.
- 5 Meijer GA, Hermsen MA, Baak JP, van Diest PJ, Meuwissen SG, Belien JA, Hoovers JM, Joenje H, Snijders PJ, Walboomers JM. Progression from colorectal adenoma to carcinoma is associated with non-random chromosomal gains as detected by comparative genomic hybridisation. J Clin Pathol 1998; 51: 901–9.
- 6 De Angelis PM, Clausen OP, Schjolberg A, Stokke T. Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes. Br J Cancer 1999; 80: 526–35.
- 7 Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S. A national cancer institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998; 58: 5248–57.
- 8 Park JG, Vasen HF, Park KJ, Peltomaki P, Ponz de Leon M, Rodriguez-Bigas MA, Lubinski J, Beck NE, Bisgaard ML, Miyaki M, Wijnen JT, Baba S, et al. Suspected hereditary nonpolyposis colorectal cancer: international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC) criteria and results of genetic diagnosis. Dis Colon Rectum 1999; 42: 710–5; discussion 5–6.
- 9 Hoglund M, Gisselsson D, Mandahl N, Johansson B, Mertens F, Mitelman F, Sall T. Multivariate analyses of genomic imbalances in solid tumors reveal distinct and converging pathways of karyotypic evolution. Genes Chromosomes Cancer 2001; 31: 156–71.
- 10
Compton C,
Fenoglio-Preiser CM,
Pettigrew N,
Fielding LP.
American joint committee on cancer prognostic factors consensus conference: colorectal working group.
Cancer
2000;
88:
1739–57.
10.1002/(SICI)1097-0142(20000401)88:7<1739::AID-CNCR30>3.0.CO;2-T CAS PubMed Web of Science® Google Scholar
- 11 Risques RA, Moreno V, Ribas M, Marcuello E, Capella G, Peinado MA. Genetic pathways and genome-wide determinants of clinical outcome in colorectal cancer. Cancer Res 2003; 63: 7206–14.
- 12 Diep CB, Thorstensen L, Meling GI, Skovlund E, Rognum TO, Lothe RA. Genetic tumor markers with prognostic impact in Dukes' stages B and C colorectal cancer patients. J Clin Oncol 2003; 21: 820–9.
- 13 Yashiro M, Carethers JM, Laghi L, Saito K, Slezak P, Jaramillo E, Rubio C, Koizumi K, Hirakawa K, Boland CR. Genetic pathways in the evolution of morphologically distinct colorectal neoplasms. Cancer Res 2001; 61: 2676–83.
- 14 Goel A, Arnold CN, Niedzwiecki D, Chang DK, Ricciardiello L, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res 2003; 63: 1608–14.
- 15 Bertucci F, Salas S, Eysteries S, Nasser V, Finetti P, Ginestier C, Charafe-Jauffret E, Loriod B, Bachelart L, Montfort J, Victorero G, Viret F, et al. Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene 2004; 23: 1377–91.
- 16 Koehler A, Bataille F, Schmid C, Ruemmele P, Waldeck A, Blaszyk H, Hartmann A, Hofstaedter F, Dietmaier W. Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage. J Pathol 2004; 204: 65–74.
- 17 Diep CB, Kleivi K, Ribeiro FR, Teixeira MR, Lindgjaerde OC, Lothe RA. The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosomes Cancer 2006; 45: 31–41.
- 18
Blaker H,
Graf M,
Rieker RJ,
Otto HF.
Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases.
J Pathol
1999;
188:
258–62.
10.1002/(SICI)1096-9896(199907)188:3<258::AID-PATH350>3.0.CO;2-9 CAS PubMed Web of Science® Google Scholar
- 19
Thorstensen L,
Qvist H,
Nesland JM,
Giercksky KE,
Lothe RA.
Allelotype profiles of local recurrences and distant metastases from colorectal-cancer patients.
Int J Cancer
1996;
69:
452–6.
10.1002/(SICI)1097-0215(19961220)69:6<452::AID-IJC6>3.0.CO;2-3 CAS PubMed Web of Science® Google Scholar
- 20 Weber JC, Schneider A, Rohr S, Nakano H, Bachellier P, Mechine A, Hamel G, Kanor M, Chenard MP, Gaub MP, Oudet P, Meyer C, et al. Analysis of allelic imbalance in patients with colorectal cancer according to stage and presence of synchronous liver metastases. Ann Surg 2001; 234: 795–802; discussion 802–3.
- 21 Canzian F, Salovaara R, Hemminki A, Kristo P, Chadwick RB, Aaltonen LA, de la Chapelle A. Semiautomated assessment of loss of heterozygosity and replication error in tumors. Cancer Res 1996; 56: 3331–7.
- 22 Schneider A, Rohr S, Kelly MD, Mitry R, Pignatelli M, Dore CJ, Gaub MP, Jaeck D, Meyer C, Oudet P, Habib NA. Microsatellite instability and allelic imbalance in primary and secondary colorectal cancer. Aust N Z J Surg 2000; 70: 587–92.
- 23 Schneider A, Borgnat S, Lang H, Regine O, Lindner V, Kassem M, Saussine C, Oudet P, Jacqmin D, Gaub MP. Evaluation of microsatellite analysis in urine sediment for diagnosis of bladder cancer. Cancer Res 2000; 60: 4617–22.
- 24 Delattre O, Olschwang S, Law DJ, Melot T, Remvikos Y, Salmon RJ, Sastre X, Validire P, Feinberg AP, Thomas G. Multiple genetic alterations in distal and proximal colorectal cancer. Lancet 1989; 2: 353–5.
- 25 De Angelis E, Grassi M, Gullick WJ, Johnson GR, Rossi GB, Tempesta A, De Angelis F, De Luca A, Salomon DS, Normanno N. Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families. Int J Oncol 1999; 14: 437–40.
- 26 Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet 2003; 33: 49–54.
- 27 Diep CB, Teixeira MR, Thorstensen L, Wiig JN, Eknaes M, Nesland JM, Giercksky KE, Johansson B, Lothe RA. Genome characteristics of primary carcinomas, local recurrences, carcinomatoses and liver metastases from colorectal cancer patients. Mol Cancer 2004; 3: 6.
- 28 Fearon ER. Colorectal cancer: molecular genetic studies and their future clinical applications. Med Pediatr Oncol Suppl 1996; 1: 35–40.
- 29 Hermsen M, Postma C, Baak J, Weiss M, Rapallo A, Sciutto A, Roemen G, Arends JW, Williams R, Giaretti W, De Goeij A, Meijer G. Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology 2002; 123: 1109–19.
- 30 Remvikos Y, Muleris M, Salmon RJ, Dutrillaux B. Colorectal carcinogenesis: from chromosomal evolution pathways to molecular pathogenesis. Cancer Genet Cytogenet 1997; 93: 63–73.
- 31 Bernards R Weinberg RA. A progression puzzle. Nature 2002; 418: 823.
- 32 Tsao JL, Tavare S, Salovaara R, Jass JR, Aaltonen LA, Shibata D. Colorectal adenoma and cancer divergence. Evidence of multilineage progression. Am J Pathol 1999; 154: 1815–24.
- 33 Jiang JK, Chen YJ, Lin CH, Yu IT, Lin JK. Genetic changes and clonality relationship between primary colorectal cancers and their pulmonary metastases–an analysis by comparative genomic hybridization. Genes Chromosomes Cancer 2005; 43: 25–36.
- 34 Roepman P, Wessels LF, Kettelarij N, Kemmeren P, Miles AJ, Lijnzaad P, Tilanus MG, Koole R, Hordijk GJ, van der Vliet PC, Reinders MJ, Slootweg PJ, et al. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet 2005; 37: 182–6.
- 35 Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004; 4: 71–8.
- 36 Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563–72.
- 37 Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J, Garner RC, Steele RJ, Wolf CR. Mutations in APC, Kirsten-ras and p53–alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci USA 2002; 99: 433–8.
- 38 Leslie A, Pratt NR, Gillespie K, Sales M, Kernohan NM, Smith G, Wolf CR, Carey FA, Steele RJ. Mutations of APC, K-ras and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas. Cancer Res 2003; 63: 4656–61.
- 39 Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Nathke IS. A role for the adenomatous polyposis coli protein in chromosome segregation. Nat Cell Biol 2001; 3: 429–32.
- 40 Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, van Es JH, Breukel C, Wiegant J, Giles RH, Clevers H. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 2001; 3: 433–8.
- 41 Rowan AJ, Lamlum H, Ilyas M, Wheeler J, Straub J, Papadopoulou A, Bicknell D, Bodmer WF, Tomlinson IP. APC mutations in sporadic colorectal tumors: a mutational “hotspot” and interdependence of the “two hits”. Proc Natl Acad Sci USA 2000; 97: 3352–7.
- 42 Crabtree M, Sieber OM, Lipton L, Hodgson SV, Lamlum H, Thomas HJ, Neale K, Phillips RK, Heinimann K, Tomlinson IP. Refining the relation between ‘first hits’ and ‘second hits’ at the APC locus: the ‘loose fit’ model and evidence for differences in somatic mutation spectra among patients. Oncogene 2003; 22: 4257–65.
Citing Literature
