Genomic analysis of breast tumors reveals three subtypes. A. Hierarchical clustering of 62 ductal invasive breast tumors and five BRCA1 mutant tumors based on their genome-wide DNA copy number profiles. Individual clones are represented as rows, ordered by chromosome and genome position according to the July 2003 freeze of the human genome. Clones on the p-arm and q-arm of chromosomes are indicated in shades of dark gray (odd numbered chromosomes) or light gray (even numbered chromosomes). Acrocentric chromosomes are shown in dark or light gray. Columns represent individual tumor samples. The estrogen receptor status of the tumors is shown in shades of blue (dark blue = ER negative, light blue = ER positive), BRCA1 mutant tumors are indicated in orange, and TP53 mutation status is indicated with a maroon box for TP53 mutant tumors, a gray box for tumors with no detected mutation and a black box if the TP53 status is unknown. Copy number losses are indicated in red, gains in green and amplifications as yellow dots. Three main clusters are evident. B-F. Genome-wide copy number aberrations profiles of sporadic and hereditary (BRCA1) breast tumors are plotted as the normalized log2ratio for each clone sorted by chromosome and ordered according to genome position from the p-arm to the q-arm. Normalized copy number ratios of genomic DNA are shown for a tumor from the 1q/16q cluster with few copy number changes including gain of 1q and loss of 16q (B), a tumor from the ER negative, complex cluster showing many low level chromosome changes and few amplifications (C), a tumor from the amplifier cluster with low level gains and losses and amplifications (D) and tumors from patients with mutations in BRCA1 (E and F). G. Numbers and types of copy number aberrations in breast tumor subtypes. The mean numbers of whole chromosome copy number changes, copy number transitions and amplifications were determined for the tumors within each subtype. H. Numbers and types of copy number aberrations in breast tumor subtypes. The mean numbers of chromosomes showing no copy number change, whole chromosome copy number changes, copy number transitions, copy number transitions at centromeres and amplifications were determined for the tumors within each subtype. I. Association with disease-specific survival. Significance of the log-rank test was used to assess the association between a genomic subclass and survival phenotypes. The significance was declared at p < 0.05. Patients with complex tumors experienced significantly worse outcome compared to the other groups.
Fridlyand et al. BMC Cancer 2006 6:96 doi:10.1186/1471-2407-6-96