CD74-NRG1 fusions in lung adenocarcinoma

Study ID Alternative Stable ID Type
EGAS00001000653 Other

Study Description

We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (p<0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.

Study Datasets 2 datasets.

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Dataset ID Description Technology Samples
RNAseq data, Publication Fernandez-Cuesta et al., 2014, CD74-NRG1 fusions in lung adenocarcinoma
Illumina HiSeq 2000 25
Fernandez-Cuesta et al., RNAseq data Pipline
Illumina HiSeq 2000 25

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