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A signature of chromosomal
instability inferred from gene expression profiles predicts clinical
outcome in multiple human cancers
Scott L
Carter1, Aron C Eklund1, 2, Isaac
S Kohane1, Lyndsay N Harris3 & Zoltan
Szallasi1, 4
1Children's
Hospital Informatics Program at the Harvard-MIT Division of Health
Sciences and Technology (CHIP@HST), Harvard Medical School, Boston,
Massachusetts 02115, USA. 2Laboratory of Functional
Genomics, Brigham and Women's Hospital, Cambridge, Massachusetts
02139, USA. 3Breast Disease Unit, Yale School of Medicine,
New Haven, Connecticut 06520-8032, USA.4Center for
Biological Sequence Analysis, Technical University of Denmark, DK-2800
Lyngby, Denmark. -- Correspondence should be
addressed to Zoltan Szallasi zszallasi@chip.org .
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We
developed a computational method to characterize aneuploidy in tumor
samples based on coordinated aberrations in expression of genes
localized to each chromosomal region.
We summarized the total level of
chromosomal aberration in a given tumor in a univariate measure termed
total functional aneuploidy.
We identified a signature of
chromosomal instability from specific genes whose expression was
consistently correlated with total functional aneuploidy in several
cancer types.
Net overexpression of this signature
was predictive of poor clinical outcome in 12 cancer data sets1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 representing six cancer
types.
Also, the signature of chromosomal
instability was higher in metastasis samples than in primary tumors
and was able to stratify grade 1 and grade 2 breast tumors according
to clinical outcome.
These results provide a means to
assess the potential role of chromosomal instability in determining
malignant potential over a broad range of tumors.
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