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Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes
Author(s) -
Weber JeanChristophe,
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 MariePierre
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22343
Subject(s) - metastasis , carcinogenesis , colorectal cancer , biology , primary tumor , tumor progression , loss of heterozygosity , cancer research , chromosome , pathology , cancer , medicine , gene , genetics , allele
Abstract 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.