Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Lost in translation: returning germline genetic results in genome-scale cancer research
Author: Johns, A.
McKay, S.
Humphris, J.
Pinese, M.
Chantrill, L.
Mead, R.
Tucker, K.
Andrews, L.
Goodwin, A.
Leonard, C.
High, H.
Nones, K.
Waddell, N.
Patch, A.
Merrett, N.
Pavlakis, N.
Kassahn, K.
Samra, J.
Miller, D.
Chang, D.
et al.
Citation: Genome Medicine, 2017; 9(1):41
Publisher: BioMed Central
Issue Date: 2017
ISSN: 1756-994X
Statement of
Amber L. Johns, Skye H. McKay, Jeremy L. Humphris, Mark Pinese, Lorraine A. Chantrill, R. Scott Mead, Katherine Tucker, Lesley Andrews, Annabel Goodwin, Conrad Leonard, Hilda A. High, Katia Nones, Ann-Marie Patch, Neil D. Merrett, Nick Pavlakis, Karin S. Kassahn, Jaswinder S. Samra, David K. Miller, David K. Chang, Marina Pajic, Australian Pancreatic Cancer Genome Initiative, John V. Pearson6, Sean M. Grimmond, Nicola Waddell, Nikolajs Zeps, Anthony J. Gill and Andrew V. Biankin
Abstract: 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.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.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.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; return of results; research ethics; whole-genome sequencing
Rights: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
RMID: 0030078189
DOI: 10.1186/s13073-017-0430-4
Grant ID:
Appears in Collections:Genetics publications

Files in This Item:
File Description SizeFormat 
hdl_110803.pdfPublished Version727.23 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.