title: Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes.
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.
authors.affiliation: Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Weber
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meyer
authors.forename: Erwan
authors.initials: E
authors.lastname: Pencreach
authors.forename: Anne
authors.initials: A
authors.lastname: Schneider
authors.forename: Eric
authors.initials: E
authors.lastname: Guérin
authors.forename: Agnès
authors.initials: A
authors.lastname: Neuville
authors.forename: Christine
authors.initials: C
authors.lastname: Stemmer
authors.forename: Cécile
authors.initials: C
authors.lastname: Brigand
authors.forename: Philippe
authors.initials: P
authors.lastname: Bachellier
authors.forename: Serge
authors.initials: S
authors.lastname: Rohr
authors.forename: Michèle
authors.initials: M
authors.lastname: Kedinger
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Dominique
authors.initials: D
authors.lastname: Guenot
authors.forename: Pierre
authors.initials: P
authors.lastname: Oudet
authors.forename: Daniel
authors.initials: D
authors.lastname: Jaeck
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gaub
mesh_terms: D000483:Alleles; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged