Journal
JOURNAL OF PATHOLOGY
Volume 220, Issue 3, Pages 338-347Publisher
WILEY
DOI: 10.1002/path.2640
Keywords
survival; colorectal cancer; microsatellite instability; array-comparative genomic hybridization; BRUNOL4; CELF4
Funding
- Addenbrooke's Charitable Trust
- John Lucas Walker Fund
- Pathological Society of Great Britain and Ireland
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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 (NISI-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. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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