@article{e80b888058e44c3d803aa5bee58caac3,
title = "Lost in translation: Returning germline genetic results in genome-scale cancer research",
abstract = "Background: The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned. Using this experience, we discuss barriers and opportunities associated with a comprehensive process of RoR in large-scale genomic research that may be useful for others developing their own policies. Methods: We performed whole-genome (n = 184) and exome (n = 208) sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline mutations in candidate genes (n = 130) with established predisposition to PC or medium-high penetrance genes with well-defined cancer associated syndromes or phenotypes. Variants from candidate genes were annotated and classified according to international guidelines. Variants were considered actionable if clinical utility was established, with regard to prevention, diagnosis, prognostication and/or therapy. Results: A total of 48,904 germline variants were identified, with 2356 unique variants undergoing annotation and in silico classification. Twenty cases were deemed actionable and were returned via previously described RoR framework, representing an actionable finding rate of 5.1%. Overall, 1.78% of our cohort experienced clinical benefit from RoR. Conclusion: Returning research results within the context of large-scale genomics research is a labour-intensive, highly variable, complex operation. Results that warrant action are not infrequent, but the prevalence of those who experience a clinical difference as a result of returning individual results is currently low.",
keywords = "Genomic data, Research ethics, Return of results, Whole-genome sequencing",
author = "{Australian Pancreatic Cancer Genome Initiative} and Johns, {Amber L.} and McKay, {Skye H.} and Humphris, {Jeremy L.} and Mark Pinese and Chantrill, {Lorraine A.} and Mead, {R. Scott} and Katherine Tucker and Lesley Andrews and Annabel Goodwin and Conrad Leonard and High, {Hilda A.} and Katia Nones and Patch, {Ann Marie} and Merrett, {Neil D.} and Nick Pavlakis and Nicola Waddell and Kassahn, {Karin S.} and Samra, {Jaswinder S} and Miller, {David K.} and Chang, {David K.} and Marina Pajic and Pearson, {John V.} and Grimmond, {Sean M.} and Nikolajs Zeps and Gill, {Anthony J.} and Biankin, {Andrew V.} and Chin, {Venessa T.} and Angela Chou and Angela Steinmann and Mehreen Arshi and Ali Drury and Danielle Froio and Ashleigh Morgan and Paul Timpson and David Hermann and Claire Vennin and Sean Warren and Jianmin Wu and Pinho, {Andreia V.} and Felicity Newell and Pamela Mukhopadhyay and Venkateswar Addala and Stephen Kazakoff and Oliver Holmes and Scott Wood and Christina Xu and Oliver Hofmann and Wilson, {Peter J.} and Angelika Christ and Tim Bruxner and Jennifer Arena and Anubhav Mittal and Ray Asghari and Darren Pavey and Amitabha Das and Cosman, {Peter H.} and Kasim Ismail and Chelsie O'Connnor and Alina Stoita and David Williams and Allan Spigellman and Lam, {Vincent W.} and Duncan McLeod and Nagrial, {Adnan M.} and Judy Kirk and Virginia James and Kench, {James G} and Peter Grimison and Cooper, {Caroline L.} and Charbel Sandroussi and Cindy Forest and Epari, {Krishna P.} and Mo Ballal and Fletcher, {David R.} and Sanjay Mukhedkar and Maria Beilin and Kynan Feeney and Nguyen, {Nan Q.} and Ruszkiewicz, {Andrew R.} and Chris Worthley and John Chen and Brooke-Smith, {Mark E.} and Virginia Papangelis and Clouston, {Andrew D.} and Patrick Martin and Barbour, {Andrew P.} and O'Rourke, {Thomas J.} and Fawcett, {Jonathan W.} and Kellee Slater and Michael Hatzifotis and Peter Hodgkinson and Mehrdad Nikfarjam and Eshleman, {James R} and Hruban, {Ralph H.} and Wolfgang, {Christopher L.} and Mary Hodgin and Lawlor, {Rita T.} and Stefania Beghelli and Vincenzo Corbo and Maria Scardoni and Claudio Bassi and Peter Bailey and Sancha Martin and Musgrove, {Elizabeth A.} and Jones, {Marc D.} and Craig Nourse and Jamieson, {Nigel B.}",
year = "2017",
month = apr,
day = "28",
doi = "10.1186/s13073-017-0430-4",
language = "English",
volume = "9",
journal = "Genome Medicine",
issn = "1756-994X",
publisher = "BioMed Central Ltd.",
number = "1",
}