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Ann Oncol. 2019 Aug 1;30(8):1221-1231. doi: 10.1093/annonc/mdz136.

Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group.

Author information

1
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York.
2
Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York.
3
Department of Clinical Genetics, St George's University of London, London.
4
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, USA.
5
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.
6
European Society for Medical Oncology (ESMO) Head Office, Lugano, Switzerland.
7
Department of Clinical Genetics, Guy and St Thomas' NHS Foundation Trust, London.
8
Department of Clinical Genetics, Oxford University Hospitals NHS Foundation Trust, Oxford.
9
Department of Health Sciences, University of Leicester, Leicester, UK.
10
University of Toulouse, Toulouse, France.
11
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
12
Cancer Genetics Unit, The Royal Marsden NHS Foundation Trust, London.
13
Division of Genetics and Epidemiology, Institute of Cancer Research, London.
14
William Harvey Research Institute, Queen Mary University of London, London.
15
Public Health England, London, UK.

Abstract

It is increasingly common in oncology practice to perform tumour sequencing using large cancer panels. For pathogenic sequence variants in cancer susceptibility genes identified on tumour-only sequencing, it is often unclear whether they are of somatic or constitutional (germline) origin. There is wide-spread disparity regarding both the extent to which systematic 'germline-focussed analysis' is carried out upon tumour sequencing data and for which variants follow-up analysis of a germline sample is carried out. Here we present analyses of paired sequencing data from 17 152 cancer samples, in which 1494 pathogenic sequence variants were identified across 65 cancer susceptibility genes. From these analyses, the European Society of Medical Oncology Precision Medicine Working Group Germline Subgroup has generated (i) recommendations regarding germline-focussed analyses of tumour-only sequencing data, (ii) indications for germline follow-up testing and (iii) guidance on patient information-giving and consent.

KEYWORDS:

gene; germline; panel; predisposition; sequencing; susceptibility

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