{"entity":{"id":"paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018","kind":"paper","name":"Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine","aka":[],"tldr":"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.","asOf":"2026-09-24","links":[{"label":"Aguirre et al., Cancer Discov 2018: real-time exome and RNA sequencing of 71 advanced patients","url":"https://doi.org/10.1158/2159-8290.CD-18-0275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29903880/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs","rna-seq","germline-testing"],"targets":["braf","brca"],"drugs":[],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":["ras-mapk","homologous-recombination-repair"],"terms":["germline-vs-somatic","hrd"],"trials":[],"people":["andrew-aguirre","david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-18-0275","pmid":"29903880","authors":"Aguirre AJ, Nowak JA, Camarda ND, et al.","paperType":"translational","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."],"whatItMeans":"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."],"changedPractice":false,"participants":71},"route":"/key-papers/paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018/","neighbours":{"cancer":[{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"},{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"pathway":[{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"}],"person":[{"id":"andrew-aguirre","kind":"person","name":"Andrew J. Aguirre","route":"/people/andrew-aguirre/"},{"id":"david-tuveson","kind":"person","name":"David A. Tuveson","route":"/people/david-tuveson/"}],"journal":[{"id":"cancer-discovery","kind":"journal","name":"Cancer Discovery","route":"/journals/cancer-discovery/"}]}}