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NRG1 Fusions in KRAS Wild-type Pancreatic Cancer (H021)

We used whole-genome and transcriptome sequencing to identify clinically actionable gene fusions in young adults with KRAS wild-type (KRASwt) pancreatic ductal adenocarcinoma (PDAC). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASwt tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of PDAC patients.

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Dataset ID Description Technology Samples
EGAD00001004068 HiSeq X Ten Illumina HiSeq 2500 Illumina HiSeq 4000 36
Publications Citations
Accurate and efficient detection of gene fusions from RNA sequencing data.
Genome Res 31: 2021 448-460