Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes

• Published in: International journal of cancer Vol. 120; no. 3; pp. 524 - 532
• Main Authors: Weber, Jean‐Christophe, Meyer, Nicolas, Pencreach, Erwan, Schneider, Anne, Guérin, Eric, Neuville, Agnès, Stemmer, Christine, Brigand, Cécile, Bachellier, Philippe, Rohr, Serge, Kedinger, Michèle, Meyer, Christian, Guenot, Dominique, Oudet, Pierre, Jaeck, Daniel, Gaub, Marie‐Pierre
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2007; Wiley-Liss
• Subjects: Alleles; allelotyping; Biological and medical sciences; Chromosome Aberrations; chromosome instability; Chromosomes, Human, Pair 17 - genetics; Chromosomes, Human, Pair 18 - genetics; Chromosomes, Human, Pair 8 - genetics; Cluster Analysis; colon cancer; Colonic Neoplasms - classification; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genomic Instability - genetics; Genotype; Humans; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Male; matched samples; Medical sciences; metastasis; Microsatellite Repeats - genetics; Middle Aged; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Malignant tumor; Metastasis; Chromosomal instability; Colonic disease; Colon cancer; Cancerology; allelotyping; Cytogenetics; Digestive diseases; Genetics; Intestinal disease; Subtype; chromosome instability; matched samples
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.22343

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.