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Study Description

Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole exome sequencing (WES) and RNA-sequencing (RNA-Seq) for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAP-kinase pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC.

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Publicly Available Data
Study Inclusion/Exclusion Criteria

Inclusion Criteria:

  • Histologically-confirmed diagnosis of pancreatic adenocarcinoma
  • Patients without prior histologic diagnosis of pancreatic cancer were eligible to enroll if PDAC was suspected based on clinical presentation and imaging studies.
  • At least 18 years old
  • ECOG performance status of 0-2
  • Ability to safely halt anticoagulation for the biopsy procedure
  • No concurrent chemotherapy treatment
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Diseases/Traits Related to Study (MeSH terms)
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Study Attribution
  • Principal Investigators
    • Brian Wolpin MD, MPH. Dana Farber Cancer Institute, Broad Institute, MA, USA.
    • Andrew Aguirre, MD, PhD. Dana Farber Cancer Institute, Broad Institute, MA, USA.
    • Scott Carter, PhD. Dana Farber Cancer Institute, Broad Institute, MA, USA.