Chromosomal instability in microsatellite-unstable and stable colon cancer.
OBJECTIVE
The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors.


METHODS
Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones.


RESULTS
MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P=0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization.


CONCLUSIONS
MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.
Trautmann
Karolin
K
Comprehensive Cancer Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143-0808, USA.
Terdiman
Jonathan P
JP
French
Amy J
AJ
Roydasgupta
Ritu
R
Sein
Nancy
N
Kakar
Sanjay
S
Fridlyand
Jane
J
Snijders
Antoine M
AM
Albertson
Donna G
DG
Thibodeau
Stephen N
SN
Waldman
Frederic M
FM
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D043171:Chromosomal Instability; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis