title: Chromosomal instability in near-diploid colorectal cancer: a link between numbers and structure.
abstract: Chromosomal instability (CIN) plays a crucial role in tumor development and occurs mainly as the consequence of either missegregation of normal chromosomes (MSG) or structural rearrangement (SR). However, little is known about the respective chromosomal targets of MSG and SR and the way these processes combined within tumors to generate CIN. To address these questions, we karyotyped a consecutive series of 96 near-diploid colorectal cancers (CRCs) and distinguished chromosomal changes generated by either MSG or SR in tumor cells. Eighty-three tumors (86%) presented with chromosomal abnormalities that contained both MSGs and SRs to varying degrees whereas all 13 others (14%) showed normal karyotype. Using a maximum likelihood statistical method, chromosomes affected by MSG or SR and likely to represent changes that are selected for during tumor progression were found to be different and mostly mutually exclusive. MSGs and SRs were not randomly associated within tumors, delineating two major pathways of chromosome alterations that consisted of either chromosome gains by MSG or chromosomal losses by both MSG and SR. CRCs showing microsatellite instability (MSI) presented with either normal karyotype or chromosome gains whereas MSS (microsatellite stable) CRCs exhibited a combination of the two pathways. Taken together, these data provide new insights into the respective involvement of MSG and SR in near-diploid colorectal cancers, showing how these processes target distinct portions of the genome and result in specific patterns of chromosomal changes according to MSI status.
authors.affiliation: French National Institute for Health and Medical Research (INSERM), UMRS_762, Centre de Recherche (CDR) Saint-Antoine, Paris, France. martine.muleris@cephb.fr
authors.forename: Martine
authors.initials: M
authors.lastname: Muleris
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chalastanis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meyer
authors.forename: Marick
authors.initials: M
authors.lastname: Lae
authors.forename: Bernard
authors.initials: B
authors.lastname: Dutrillaux
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Richard
authors.initials: R
authors.lastname: Hamelin
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Alex
authors.initials: A
authors.lastname: Duval
mesh_terms: D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004171:Diploidy; D018450:Disease Progression; D006801:Humans; D007621:Karyotyping; D016013:Likelihood Functions