The mutational landscape of theSCAN‐B real‐world primary breast cancer transcriptome

Abstract

Breast cancer is a disease of genomic alterations, of which the panorama of somatic mutations and how these relate to subtypes and therapy response is incompletely understood. Within SCAN-B (ClinicalTrials.gov: NCT02306096), a prospective study elucidating the transcriptomic profiles for thousands of breast cancers, we developed a RNA-seq pipeline for detection of SNVs/indels and profiled a real-world cohort of 3,217 breast tumors. We describe the mutational landscape of primary breast cancer viewed through the transcriptome of a large population-based cohort and relate it to patient survival. We demonstrate that RNA-seq can be used to call mutations in genes such as PIK3CA, TP53, and ERBB2, as well as the status of molecular pathways and mutational burden, and identify potentially druggable mutations in 86.8% of tumors. To make this rich dataset available for the research community, we developed an open source web application, the SCAN-B MutationExplorer (http://oncogenomics.bmc.lu.se/MutationExplorer). These results add another dimension to the use of RNA-seq as a clinical tool, where both gene expression-and mutation-based biomarkers can be interrogated in real-time within 1 week of tumor sampling.

Serum selenium, selenoprotein P and glutathione peroxidase 3 as predictors of mortality and recurrence following breast cancer diagnosis: A multicentre cohort study

“…The Sweden Cancerome Analysis Network - Breast Initiative (SCAN-B) ( ClinicalTrials.gov ID NCT02306096 ) is a prospective real-world, population based multicentre study enrolling patients since August 30th, 2010. It aims to identify new prognostic factors and targets for individualized therapy by genomic profiling of breast cancer [ [27] , [28] , [29] ]. Patients treated in the participating hospitals in Malmö, Lund, Helsingborg, Kristianstad, Växjö, Halmstad, Uppsala, Karlskrona, Varberg, and Ljungby were included in the analyses.…”

Bioinformatics reveal macrophages marker genes signature in breast cancer to predict prognosis

“…Individual patient files and mRNA expression raw data were obtained from TCGA data portal ( https://portal.gdc.cancer.gov/ ). To validate the prognostic ability of the constructed model, normalized RNA sequencing data in the form of log 2 (FPKM + 0.1) was downloaded from GSE96058 dataset ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96058 ) [ 24 , 25 ]. DNA methylation raw data were obtained from TCGA data portal.…”

Enhanced Thermogenesis in Triple-Negative Breast Cancer Is Associated with Pro-Tumor Immune Microenvironment

“…The GSE96058 cohort has the transcriptome profiling of 3273 resected breast cancers from an ongoing study. The latest publicly available clinical data of these patients were obtained from resources noted in a recent The Sweden Cancerome Analysis Network-Breast (SCAN-B) study [ 20 ], with 143 TNBC cases. The published data of Shi et al (GSE20194, n = 68) [ 21 ] and Symmans et al (GSE25066, n = 170) [ 22 ] were used to investigate the association of the thermogenesis scores with treatment response to neoadjuvant chemotherapy (NAC).…”

“…The published data of Shi et al (GSE20194, n = 68) [ 21 ] and Symmans et al (GSE25066, n = 170) [ 22 ] were used to investigate the association of the thermogenesis scores with treatment response to neoadjuvant chemotherapy (NAC). The analysis shown in this paper was performed within each cohort, and normalization within each cohort was conducted at the time of original publication [ 17 , 19 , 20 , 21 , 22 ]. Disease-free survival (DFS) was defined as the time from primary treatment completion until clinical confirmation of disease recurrence or death.…”