Genome-wide multi-omics profiling of the 8p11-p12 amplicon in breast carcinoma.

Parris TZ, Rönnerman EW, Engqvist H, Biermann J, Truvé K, Nemes S, Forssell-Aronsson E, Solinas G, Kovács A, Karlsson P, Helou K

Oncotarget 9 (35) 24140-24154 [2018-05-08; online 2018-05-08]

Genomic instability contributes to the neoplastic phenotype by deregulating key cancer-related genes, which in turn can have a detrimental effect on patient outcome. DNA amplification of the 8p11-p12 genomic region has clinical and biological implications in multiple malignancies, including breast carcinoma where the amplicon has been associated with tumor progression and poor prognosis. However, oncogenes driving increased cancer-related death and recurrent genetic features associated with the 8p11-p12 amplicon remain to be identified. In this study, DNA copy number and transcriptome profiling data for 229 primary invasive breast carcinomas (corresponding to 185 patients) were evaluated in conjunction with clinicopathological features to identify putative oncogenes in 8p11-p12 amplified samples. Illumina paired-end whole transcriptome sequencing and whole-genome SNP genotyping were subsequently performed on 23 samples showing high-level regional 8p11-p12 amplification to characterize recurrent genetic variants (SNPs and indels), expressed gene fusions, gene expression profiles and allelic imbalances. We now show previously undescribed chromothripsis-like patterns spanning the 8p11-p12 genomic region and allele-specific DNA amplification events. In addition, recurrent amplification-specific genetic features were identified, including genetic variants in the

Bioinformatics Compute and Storage [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

QC bibliography QC xrefs

PubMed 29844878

DOI 10.18632/oncotarget.25329

Crossref 10.18632/oncotarget.25329

pii: 25329
pmc: PMC5963621
GEO: GSE97293 Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas