Back to Search
Start Over
Uncovering Clinically Relevant Gene Fusions with Integrated Genomic and Transcriptomic Profiling of Metastatic Cancers
- Source :
- Clinical Cancer Research. 27:522-531
- Publication Year :
- 2021
- Publisher :
- American Association for Cancer Research (AACR), 2021.
-
Abstract
- Purpose:Gene fusions are important oncogenic drivers and many are actionable. Whole-genome and transcriptome (WGS and RNA-seq, respectively) sequencing can discover novel clinically relevant fusions.Experimental Design:Using WGS and RNA-seq, we reviewed the prevalence of fusions in a cohort of 570 patients with cancer, and compared prevalence to that predicted with commercially available panels. Fusions were annotated using a consensus variant calling pipeline (MAVIS) and required that a contig of the breakpoint could be constructed and supported from ≥2 structural variant detection approaches.Results:In 570 patients with advanced cancer, MAVIS identified 81 recurrent fusions by WGS and 111 by RNA-seq, of which 18 fusions by WGS and 19 by RNA-seq were noted in at least 3 separate patients. The most common fusions were EML4-ALK in thoracic malignancies (9/69, 13%), and CMTM8-CMTM7 in colorectal cancer (4/73, 5.5%). Combined genomic and transcriptomic analysis identified novel fusion partners for clinically relevant genes, such as NTRK2 (novel partners: SHC3, DAPK1), and NTRK3 (novel partners: POLG, PIBF1).Conclusions:Utilizing WGS/RNA-seq facilitates identification of novel fusions in clinically relevant genes, and detected a greater proportion than commercially available panels are expected to find. A significant benefit of WGS and RNA-seq is the innate ability to retrospectively identify variants that becomes clinically relevant over time, without the need for additional testing, which is not possible with panel-based approaches.
- Subjects :
- 0301 basic medicine
Cancer Research
Oncogene Proteins, Fusion
Colorectal cancer
Computational biology
Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
Neoplasms
Exome Sequencing
medicine
Humans
RNA-Seq
Neoplasm Metastasis
Gene
Retrospective Studies
Contig
Gene Expression Profiling
Breakpoint
Structural variant
Genomics
medicine.disease
Advanced cancer
3. Good health
Treatment Outcome
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Gene Fusion
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....10d10432e20718c47bd56e856e08df7e