The landscape of kinase fusions in cancer

By Nicolas Stransky, Ethan G. Cerami, S. Schalm, Joseph L. Kim, Christoph Lengauer. Nature Communications, 2014

890 citations recorded by the source corpus.

Human cancer genomes harbour a variety of alterations leading to the deregulation of key pathways in tumour cells. The genomic characterization of tumours has uncovered numerous genes recurrently mutated, deleted or amplified, but gene fusions have not been characterized as extensively. Here we develop heuristics for reliably detecting gene fusion events in RNA-seq data and apply them to nearly 7,000 samples from The Cancer Genome Atlas. We thereby are able to discover several novel and recurrent fusions involving kinases. These findings have immediate clinical implications and expand the therapeutic options for cancer patients, as approved or exploratory drugs exist for many of these kinases. Kinases activated by gene fusions represent potentially important targets for the development of cancer drugs. Here, the authors develop a method for detecting gene fusion events in RNA sequencing data from The Cancer Genome Atlas and identify several novel recurrent fusions involving kinases.

Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/22e6247a08af366f7f19620c7fc58a5b5d861d4d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Oncology

In Pulmonary and Respiratory Medicine

Citations in the corpus

Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “Somatic fusions involving the neurotropic tropomyosin receptor kinase genes (NTRK1-3) are rare oncogenic drivers occurring at low prevalence (< 1%) in a variety of tumours including NSCLC [252], again typically in adenocarcinomas (although non-adenocarcinoma cases are reported) and never-smokers.”
SpeedSeq: Ultra-fast personal genome analysis and interpretation (2014, methodology): “[32]”
Lung cancer: Biology and treatment options. (2015, background): “In lung adenocarcinomas (513 samples), fusion events were found in ROS1, RET, PRKCB, NTRK, MET and ALK genes and were found in PRKCB, PRKCA, PKN1, FGR, FGFR1, FGFR2 an FGFR3 genes in lung squamous cell carcinomas (492 samples) (Table 5) [11].”
Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children (2018, background): “A total of 13% of the patients (7 patients) had a complete response, 62% (34) had a partial response, 13% (7) had stable disease, 9% (5) had progressive disease, and 4% (2) could not be evaluated owing to early withdrawal for clinical deterioration.”
Genomic basis for RNA alterations in cancer (2020, background): “Many cancer genes (such as MET 51,52 ) are known to be somatically altered by heterogeneous mechanisms such as gene fusions, splicing mutations and non-synonymous mutations; therefore, examining genes that are altered by several cis -acting mechanisms may help to identify cancer genes in which an in”
Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods (2019, background): “Chromosomal rearrangements leading to the formation of fusion transcripts are a frequent driver in certain cancer types, including leukemia and prostate cancer [1], and contribute to many others [2].”
Mechanisms of receptor tyrosine kinase activation in cancer (2018, positive): “Likewise, oncogenic tyrosine kinase fusions involving ROS1 have been identified in ~ 1% of NSCLCs [112], as well as in IMTs, cholangiocarcinoma, and GBM [94, 113].”
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma (2017, positive): “Blueprint Medicines:Gene fusions in the LIHCdataset were discovered usingmethods previously described (Stransky et al., 2014).”
A survey of best practices for RNA-seq data analysis (2016, background): “Thus, high confidence predictions have fusion boundaries coincident with exon boundaries and exons matching wild-type exons [91].”