TY - JOUR
T1 - The mutational landscape of the SCAN‐B real‐world primary breast cancer transcriptome
AU - Brueffer, Christian
AU - Gladchuk, Sergii
AU - Winter, Christof
AU - Vallon-Christersson, Johan
AU - Hegardt, Cecilia
AU - Häkkinen, Jari
AU - George, Anthony
AU - Chen, Yilun
AU - Ehinger, Anna
AU - Larsson, Christer
AU - Loman, Niklas
AU - Malmberg, Martin
AU - Ryden, Lisa
AU - Borg, Åke
AU - Saal, Lao
PY - 2020/9/14
Y1 - 2020/9/14
N2 - 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.
AB - 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.
KW - cancer
KW - breast cancer
KW - mutation
KW - RNA-seq
KW - survival
KW - transcriptome
UR - https://oncogenomics.bmc.lu.se/MutationExplorer/
UR - https://doi.org/10.1101/2020.01.30.926733
U2 - 10.15252/emmm.202012118
DO - 10.15252/emmm.202012118
M3 - Article
C2 - 32926574
SN - 1757-4684
VL - 12
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 10
M1 - e12118
ER -