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

James Hicks, Alexander Krasnitz, B. Lakshmi, Nicholas E. Navin, Michael Riggs, Evan Leibu, Diane Esposito, Joan Alexander, Jen Troge, Vladimir Grubor, Seungtai Yoon, Michael Wigler, Kenny Ye, Anne Lise Børresen-Dale, Bjørn Naume, Ellen Schlicting, Larry Norton, Torsten Hägerström, Lambert Skoog, Gert AuerSusanne Månér, Pär Lundin, Anders Zetterberg

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254 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1465-1479
Number of pages15
JournalGenome research
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2006

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Hicks, J., Krasnitz, A., Lakshmi, B., Navin, N. E., Riggs, M., Leibu, E., Esposito, D., Alexander, J., Troge, J., Grubor, V., Yoon, S., Wigler, M., Ye, K., Børresen-Dale, A. L., Naume, B., Schlicting, E., Norton, L., Hägerström, T., Skoog, L., ... Zetterberg, A. (2006). Novel patterns of genome rearrangement and their association with survival in breast cancer. Genome research, 16(12), 1465-1479. https://doi.org/10.1101/gr.5460106