Prognostic relevance of DNA copy number changes in colorectal cancer.
In a study of 109 colorectal cancers, DNA copy number aberrations were identified by comparative genomic hybridization using a DNA microarray covering the entire genome at an average interval of less than 1 Mbase. Four patterns were revealed by unsupervised clustering analysis, one of them associated with significantly better prognosis than the others. This group contained tumours with short, dispersed, and relatively few regions of copy number gain or loss. The good prognosis of this group was not attributable to the presence of tumours showing microsatellite instability (MSI-H). Supervised methods were employed to determine those genomic regions where copy number alterations correlate significantly with multiple indices of aggressive growth (lymphatic spread, recurrence, and early death). Multivariate analysis identified DNA copy number loss at 18q12.2, harbouring a single gene, BRUNOL4 that encodes the Bruno-like 4 splicing factor, as an independent prognostic indicator. The data show that the different patterns of DNA copy number alterations in primary tumours reveal prognostic information and can aid identification of novel prognosis-associated genes.
Poulogiannis
George
G
Department of Pathology, University of Cambridge, Cambridge, UK.
Ichimura
Koichi
K
Hamoudi
Rifat A
RA
Luo
Feijun
F
Leung
Suet Y
SY
Yuen
Siu T
ST
Harrison
David J
DJ
Wyllie
Andrew H
AH
Arends
Mark J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence
D004273:DNA, Neoplasm