Establishing a Framework for the Clinical Translation of Germline Findings in Precision Oncology. Issue 5 (29th May 2020)

• Record Type: Journal Article
• Authors: Dixon, Katherine; Young, Sean; Shen, Yaoqing; Thibodeau, My Linh; Fok, Alexandra; Pleasance, Erin; Zhao, Eric; Jones, Martin; Aubert, Geraldine; Armstrong, Linlea; Virani, Alice; Regier, Dean; Gelmon, Karen; Renouf, Dan; Chia, Stephen; Bosdet, Ian; Rassekh, S Rod; Deyell, Rebecca J; Yip, Stephen; Fisic, Ana; Titmuss, Emma; Abadi, Shirin; Jones, Steven J M; Sun, Sophie; Karsan, Aly; Marra, Marco; Laskin, Janessa; Lim, Howard; Schrader, Kasmintan A
• Is Part Of: JNCI cancer spectrum. Volume 4:Issue 5(2020)
• Publication Date: 2020-05-29
• DOI: 10.1093/jncics/pkaa045
• Languages: English
• ISSNs: 2515-5091

Abstract

Abstract: Inherited genetic variation has important implications for cancer screening, early diagnosis, and disease prognosis. A role for germline variation has also been described in shaping the molecular landscape, immune response, microenvironment, and treatment response of individual tumors. However, there is a lack of consensus on the handling and analysis of germline information that extends beyond known or suspected cancer susceptibility in large-scale cancer genomics initiatives. As part of the Personalized OncoGenomics program in British Columbia, we performed whole-genome and transcriptome sequencing in paired tumor and normal tissues from advanced cancer patients to characterize the molecular tumor landscape and identify putative targets for therapy. Overall, our experience supports a multidisciplinary and integrative approach to germline data management. This includes a need for broader definitions and standardized recommendations regarding primary and secondary germline findings in precision oncology. Here, we propose a framework for identifying, evaluating, and returning germline variants of potential clinical significance that may have indications for health management beyond cancer risk reduction or prevention in patients and their families.