# Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine

Source: https://onco.cc/key-papers/paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018/  
OnCo record `paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A Boston programme biopsied and sequenced 71 patients with advanced pancreatic cancer fast enough to change treatment in 30%, finding a treatable alteration in half and an inherited one in almost one in five.

## Summary

A biopsy protocol delivered time-sensitive whole-exome and RNA sequencing for patients with advanced pancreatic ductal adenocarcinoma. Therapeutically relevant genomic alterations were identified in 48% (34 of 71) and pathogenic or likely pathogenic germline alterations in 18% (13 of 71); 30% (21 of 71) had a change in management as a result. Twenty-six patients had germline and/or somatic DNA-damage repair alterations and five more had homologous recombination deficiency signatures without an identified cause. Two patients had oncogenic in-frame BRAF deletions, with the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Tumour and stroma expression signatures with clinical relevance were identified.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Cancer Discovery
- Year: 2018
- DOI: 10.1158/2159-8290.CD-18-0275
- Authors: Aguirre AJ, Nowak JA, Camarda ND, et al.
- Findings: Actionable alterations 48%, germline 18%, management changed in 30%.; 26 with DNA-damage repair alterations plus 5 with an HRD signature and no cause.; In-frame BRAF deletions respond to MAPK inhibition.
- What it means: Together with COMPASS it made sequencing at diagnosis of advanced disease a standard expectation, and it found the BRAF-deletion class that a hotspot test misses.
- Caveats: Single academic centre with a dedicated biopsy team.; Management change does not equal survival benefit.

## Sources

- Aguirre et al., Cancer Discov 2018: real-time exome and RNA sequencing of 71 advanced patients: https://doi.org/10.1158/2159-8290.CD-18-0275
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29903880/

## Connected records

- cancers: [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [BRAF](https://onco.cc/targets/braf/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/)
- pathways: [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/)
- people: [Andrew J. Aguirre](https://onco.cc/people/andrew-aguirre/), [David A. Tuveson](https://onco.cc/people/david-tuveson/)
- journals: [Cancer Discovery](https://onco.cc/journals/cancer-discovery/)

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