Author:
Hicks James,Krasnitz Alexander,Lakshmi B.,Navin Nicholas E.,Riggs Michael,Leibu Evan,Esposito Diane,Alexander Joan,Troge Jen,Grubor Vladimir,Yoon Seungtai,Wigler Michael,Ye Kenny,Børresen-Dale Anne-Lise,Naume Bjørn,Schlicting Ellen,Norton Larry,Hägerström Torsten,Skoog Lambert,Auer Gert,Månér Susanne,Lundin Pär,Zetterberg Anders
Abstract
Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of ∼50 kb. We have used this technique to examine 243 breast tumors from two separate studies for which detailed clinical data were available. The very high resolution of this technology has enabled us to identify three characteristic patterns of genomic copy number variation in diploid tumors and to measure correlations with patient survival. One of these patterns is characterized by multiple closely spaced amplicons, or “firestorms,” limited to single chromosome arms. These multiple amplifications are highly correlated with aggressive disease and poor survival even when the rest of the genome is relatively quiet. Analysis of a selected subset of clinical material suggests that a simple genomic calculation, based on the number and proximity of genomic alterations, correlates with life-table estimates of the probability of overall survival in patients with primary breast cancer. Based on this sample, we generate the working hypothesis that copy number profiling might provide information useful in making clinical decisions, especially regarding the use or not of systemic therapies (hormonal therapy, chemotherapy), in the management of operable primary breast cancer with ostensibly good prognosis, for example, small, node-negative, hormone-receptor-positive diploid cases.
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics(clinical),Genetics
Cited by
279 articles.
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