title: Novel patterns of genome rearrangement and their association with survival in breast cancer.
abstract: 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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. hicks@cshl.edu
authors.forename: James
authors.initials: J
authors.lastname: Hicks
authors.forename: Alexander
authors.initials: A
authors.lastname: Krasnitz
authors.forename: B
authors.initials: B
authors.lastname: Lakshmi
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Navin
authors.forename: Michael
authors.initials: M
authors.lastname: Riggs
authors.forename: Evan
authors.initials: E
authors.lastname: Leibu
authors.forename: Diane
authors.initials: D
authors.lastname: Esposito
authors.forename: Joan
authors.initials: J
authors.lastname: Alexander
authors.forename: Jen
authors.initials: J
authors.lastname: Troge
authors.forename: Vladimir
authors.initials: V
authors.lastname: Grubor
authors.forename: Seungtai
authors.initials: S
authors.lastname: Yoon
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
authors.forename: Kenny
authors.initials: K
authors.lastname: Ye
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.forename: Ellen
authors.initials: E
authors.lastname: Schlicting
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Torsten
authors.initials: T
authors.lastname: Hägerström
authors.forename: Lambert
authors.initials: L
authors.lastname: Skoog
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Susanne
authors.initials: S
authors.lastname: Månér
authors.forename: Pär
authors.initials: P
authors.lastname: Lundin
authors.forename: Anders
authors.initials: A
authors.lastname: Zetterberg
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm