TY - JOUR
T1 - Somatic cancer variant curation and harmonization through consensus minimum variant level data
AU - on behalf of the ClinGen Somatic Cancer Working Group
AU - Ritter, Deborah I.
AU - Roychowdhury, Sameek
AU - Roy, Angshumoy
AU - Rao, Shruti
AU - Landrum, Melissa J.
AU - Sonkin, Dmitriy
AU - Shekar, Mamatha
AU - Davis, Caleb F.
AU - Hart, Reece K.
AU - Micheel, Christine
AU - Weaver, Meredith
AU - Van Allen, Eliezer M.
AU - Parsons, Donald W.
AU - McLeod, Howard L.
AU - Watson, Michael S.
AU - Plon, Sharon E.
AU - Kulkarni, Shashikant
AU - Madhavan, Subha
N1 - Funding Information:
ClinGen is funded by the National Human Genome Research Institute, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (U41 HG006834, U01 HG007436, U01 HG007437, HHSN261200800001E). ClinVar is supported by the Intramural Research Program of the NIH, National Library of Medicine. Additional funding: 01HG008390 (NHGRI, BD2K Program) to SM; U01HG006492 and K08CA188615 to EMV. The BASIC3 study is a Clinical Sequencing Exploratory Research (CSER) program project supported by NHGRI/NCI 1U01HG006485 to AR, SEP, and DWP.
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/11/4
Y1 - 2016/11/4
N2 - Background: To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods: We developed MVLD through a consensus approach by i) reviewing clinical actionability interpretations from institutions participating in the WG, ii) conducting extensive literature search of clinical somatic interpretation schemas, and iii) survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP), can be incorporated into MVLD. Results: Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions: We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of somatic variants to ClinVar, all of which will enhance translation to clinical oncology practice.
AB - Background: To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods: We developed MVLD through a consensus approach by i) reviewing clinical actionability interpretations from institutions participating in the WG, ii) conducting extensive literature search of clinical somatic interpretation schemas, and iii) survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP), can be incorporated into MVLD. Results: Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions: We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of somatic variants to ClinVar, all of which will enhance translation to clinical oncology practice.
KW - Cancer genomics
KW - Data standard
KW - Somatic variant curation
KW - Somatic variant interpretation
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U2 - 10.1186/s13073-016-0367-z
DO - 10.1186/s13073-016-0367-z
M3 - Article
C2 - 27814769
AN - SCOPUS:84997207493
SN - 1756-994X
VL - 8
JO - Genome Medicine
JF - Genome Medicine
IS - 1
M1 - 117
ER -