Dataset Information

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

ABSTRACT: Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC?=?0.95;AUC(replication)?=?0.97) and HER2 status (AUC?=?0.97;AUC(replication)?=?0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC?=?0.98;AUC(replication)?=?0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkers.

SUBMITTER: Rantalainen M

PROVIDER: S-EPMC5128815 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

Rantalainen Mattias M Klevebring Daniel D Lindberg Johan J Ivansson Emma E Rosin Gustaf G Kis Lorand L Celebioglu Fuat F Fredriksson Irma I Czene Kamila K Frisell Jan J Hartman Johan J Bergh Jonas J Grönberg Henrik H

Scientific reports 20161130

Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed mod ...[more]

PMID: 27901097

Similar Datasets

Project description:BackgroundNext-generation sequencing (NGS) has changed genomics significantly. More and more applications strive for sequencing with different platforms. Now, in 2012, after a decade of development and evolution, NGS has been accepted for a variety of research fields. Determination of sequencing errors is essential in order to follow next-generation sequencing beyond research use only. This study describes the overall 454 system performance of using multiple GS Junior runs with an in-house established and validated diagnostic assay for human leukocyte antigen (HLA) exon sequencing. Based on this data, we extracted, evaluated and characterized errors and variants of 60 HLA loci per run with respect to their adjacencies.ResultsWe determined an overall error rate of 0.18% in a total of 118,484,408 bases. 31.3% of all reads analyzed (n=349,503) contain one or more errors. The largest group are deletions that account for 50% of the errors. Incorrect bases are not distributed equally along sequences and tend to be more frequent at sequence ends. Certain sequence positions in the middle or at the beginning of the read accumulate errors. Typically, the corresponding quality score at the actual error position is lower than the adjacent scores.ConclusionsHere we present the first error assessment in a human next-generation sequencing diagnostics assay in an amplicon sequencing approach. Improvements of sequence quality and error rate that have been made over the years are evident and it is shown that both have now reached a level where diagnostic applications become feasible. Our presented data are better than previously published error rates and we can confirm and quantify the often described relation of homopolymers and errors. Nevertheless, a certain depth of coverage is needed, in particular with challenging areas of the sequencing target. Furthermore, the usage of error correcting tools is not essential but might contribute towards the capacity and efficiency of a sequencing run.

Dataset Information

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

Publications

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets