{"entity":{"id":"paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","kind":"paper","name":"Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms","aka":[],"tldr":"Offering a 76-gene inherited-risk test to 615 consecutive pancreatic tumour patients at Memorial Sloan Kettering found a pathogenic variant in one in five, more than 40% of whom would not have qualified for testing under the guidelines of the time.","summary":"615 unselected patients with exocrine pancreatic neoplasms consented to somatic tumour and matched normal profiling of 410 to 468 genes; germline testing of 76 susceptibility genes was performed in an identified manner in 356 and anonymised in 259. Pathogenic germline alterations were present in 122 (19.8%) across 24 genes including BRCA1/2, ATM, PALB2 and other DNA damage response genes; 41.8% did not meet then-current testing guidelines. Median overall survival did not differ by germline status (50.8 months carriers). Loss of heterozygosity was found in 60.0% of BRCA1/2 tumours. The alterations were judged therapeutically actionable in about 5 to 10% of patients.","asOf":"2026-09-24","links":[{"label":"Lowery et al., JNCI 2018: prospective germline testing of 615 exocrine pancreatic neoplasms (MSK)","url":"https://doi.org/10.1093/jnci/djy024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29506128/"}],"tags":[],"related":["brca-germline"],"cancers":["pancreatic","brca-palb2-pdac"],"sections":[],"technologies":["germline-testing"],"targets":["brca","atm","palb2"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["gbrca-mutation","vus"],"trials":[],"people":["maeve-lowery","eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2018,"doi":"10.1093/jnci/djy024","pmid":"29506128","authors":"Lowery MA, Wong W, Jordan EJ, et al.","paperType":"observational","findings":["Pathogenic germline alteration in 19.8% of 615 on a 76-gene panel.","41.8% of carriers outside testing guidelines; 60% of BRCA1/2 tumours showed loss of heterozygosity."],"whatItMeans":"The broad-panel figure: one patient in five carries something inheritable, and about one in fifteen carries something treatable.","caveats":["Includes non-ductal exocrine neoplasms; 76 genes include moderate-penetrance genes.","Single tertiary centre."],"changedPractice":true,"participants":615},"route":"/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/","neighbours":{"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"}],"cancer":[{"id":"brca-palb2-pdac","kind":"cancer","name":"BRCA or PALB2-mutant pancreatic ductal adenocarcinoma","route":"/cancers/brca-palb2-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/"}],"target":[{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"palb2","kind":"target","name":"PALB2","route":"/targets/palb2/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","route":"/terms/vus/"}],"person":[{"id":"eileen-oreilly","kind":"person","name":"Eileen M. O'Reilly","route":"/people/eileen-oreilly/"},{"id":"maeve-lowery","kind":"person","name":"Maeve Lowery","route":"/people/maeve-lowery/"}],"journal":[{"id":"jnci","kind":"journal","name":"JNCI: Journal of the National Cancer Institute","route":"/journals/jnci/"}]}}