Home
/
Data resources
/
Literature
/
23284754
Micro-scale genomic DNA copy number aberrations as another means of mutagenesis in breast cancer.

PLoS One, 2012;7(12):e51719.

Chao HH[1], He X, Parker JS, Zhao W, Perou CM

Affiliations

PMID: 23284754DOI: 10.1371/journal.pone.0051719

Impact factor: 3.752

Abstract
introduction: In breast cancer, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations, as shown by a previously described micro-deletion event in the PTEN gene in the Basal-like SUM149 breast cancer cell line.
methods: We sought to identify if small regions of genomic DNA copy number changes exist by using a high density, gene-centric Comparative Genomic Hybridizations (CGH) array on cell lines and primary tumors. A custom tiling array for CGH (244,000 probes, 200 bp tiling resolution) was created to identify small regions of genomic change, which was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments were called micro-aberrations (<64 contiguous probes, ~ 15 kb).
results: Our data showed that primary tumor breast cancer genomes frequently contained many small-scale copy number gains and losses, termed micro-aberrations, most of which are undetectable using typical-density genome-wide aCGH arrays. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5' regions of the affected genes, including the promoter region, and high frequency of micro-aberrations was associated with poor survival.
conclusion: Using a high-probe-density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that can contribute to gene inactivation. These events may contribute to tumor formation through mechanisms not detected using conventional DNA copy number analyses.
MeSH terms
Biomarkers, Tumor; Breast Neoplasms; Comparative Genomic Hybridization; DNA Copy Number Variations; Female; Gene Expression Profiling; Genome, Human; Genomic Instability; Humans; Mutagenesis; Mutation; Oligonucleotide Array Sequence Analysis; Prognosis; Survival Rate
More resources
EndNote: Download