Novel patterns of genome rearrangement and their association with survival in breast cancer

Hicks, J. B., Krasnitz, A., Lakshmi, B., Navin, N. E., Riggs, M., Leibu, E., Esposito, D., Alexander, J., Troge, J. E., Grubor, V., Yoon, S., Wigler, M. H., Ye, K., Borresen-Dale, A. L., Naume, B., Schlicting, E., Norton, L., Hagerstrom, T., Skoog, L., Auer, G., Månér, S., Lundin, P., Zetterberg, A. (December 2006) Novel patterns of genome rearrangement and their association with survival in breast cancer. Genome Research, 16 (12). pp. 1465-79. ISSN 1088-9051

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DOI: 10.1101/gr.5460106


Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of approximately 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.

Item Type: Paper
Uncontrolled Keywords: Breast Neoplasms genetics mortality pathology DNA Neoplasm genetics Diploidy Female Gene Amplification Gene Dosage Gene Expression Profiling Gene Rearrangement Genome Human Genomics Humans In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis Prognosis Retrospective Studies Survival Analysis
Subjects: organs, tissues, organelles, cell types and functions > organs types and functions > breast
diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: CSHL labs > Hicks lab
CSHL labs > Krasnitz lab
CSHL labs > Wigler lab
School of Biological Sciences > Publications
Depositing User: Editor Margaret Fantz
Date: December 2006
Date Deposited: 24 Feb 2012 16:06
Last Modified: 07 Jan 2019 19:25
PMCID: PMC1665631
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