Novel patterns of genome rearrangement and their association with survival in breast cancer.
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.
Hicks
James
J
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. hicks@cshl.edu
Krasnitz
Alexander
A
Lakshmi
B
B
Navin
Nicholas E
NE
Riggs
Michael
M
Leibu
Evan
E
Esposito
Diane
D
Alexander
Joan
J
Troge
Jen
J
Grubor
Vladimir
V
Yoon
Seungtai
S
Wigler
Michael
M
Ye
Kenny
K
Børresen-Dale
Anne-Lise
AL
Naume
Bjørn
B
Schlicting
Ellen
E
Norton
Larry
L
Hägerström
Torsten
T
Skoog
Lambert
L
Auer
Gert
G
Månér
Susanne
S
Lundin
Pär
P
Zetterberg
Anders
A
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
D004273:DNA, Neoplasm