The mutational landscape of the SCAN‐B real‐world primary breast cancer transcriptome
| Autor: | Jari Häkkinen, Cecilia Hegardt, Niklas Loman, Johan Vallon-Christersson, Lisa Rydén, Anthony M. George, Christian Brueffer, Christer Larsson, Lao H. Saal, Christof Winter, Sergii Gladchuk, Martin Malmberg, Yilun Chen, Åke Borg, Anna Ehinger |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Medicine (General) DNA Mutational Analysis RNA-Seq Breast Neoplasms Computational biology Disease Biology Oncogenomics QH426-470 survival Chromatin Epigenetics Genomics & Functional Genomics Transcriptome 03 medical and health sciences 0302 clinical medicine Breast cancer R5-920 breast cancer Report medicine Genetics Biomarkers Tumor Humans Prospective Studies Prospective cohort study Cancer medicine.disease 030104 developmental biology Mutation Molecular Medicine Medical genetics RNA‐seq Female 030217 neurology & neurosurgery Reports |
| Zdroj: | EMBO Molecular Medicine EMBO Molecular Medicine, Vol 12, Iss 10, Pp n/a-n/a (2020) |
| ISSN: | 1757-4684 1757-4676 |
| Popis: | 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. A bioinformatics pipeline was developed for detection of single nucleotide variants and small insertions/deletions from RNA sequencing (RNA‐seq) data. The mutational landscape of 3,217 primary breast cancer transcriptomes in relation to patient survival was made available through a public web portal. |
| Databáze: | OpenAIRE |
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