title: A classification system for clinical relevance of somatic variants identified in molecular profiling of cancer.
abstract: OBJECTIVE
  Interpretation systems for clinical laboratory reporting of genetic variants for inherited conditions have been widely published. By contrast, there are no existing systems for interpretation and classification of somatic variants found from molecular testing of cancer.
  
  
  METHODS
  We designed an assessment protocol and classification system for somatic variants identified through next-generation sequencing molecular profiling of tumor-derived samples and applied these to a pilot dataset of somatic variants found by next-generation sequencing profiling of 158 tumor samples derived from advanced cancer patients examined at the Princess Margaret Cancer Centre.
  
  
  RESULTS
  We present a classification system to interpret the significance of genetic variants in molecular analysis of cancer, including the following key factors: (i) known or predicted pathogenicity of the variant; (ii) primary site and tumor histology in which the variant is found; (iii) recurrence of the variant; and (iv) evidence of clinical actionability. We used these factors to develop a five-category somatic variant classification for simplified reporting of variant interpretations to treating oncologists.
  
  
  CONCLUSIONS
  Our somatic variant classification can be of practical value to other clinical molecular laboratories performing cancer genetic profiling by promoting consistent reporting of somatic variants and permitting harmonization of variant data among laboratories and clinical studies.
authors.affiliation: Laboratory Medicine Program, Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Mahadeo A
authors.identifier: http://orcid.org/0000-0002-9122-2519
authors.initials: MA
authors.lastname: Sukhai
authors.affiliation: Laboratory Medicine Program, Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Craddock
authors.affiliation: Laboratory Medicine Program, Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Mariam
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Hansen
authors.affiliation: Laboratory Medicine Program, Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Lillian
authors.initials: L
authors.lastname: Siu
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bedard
authors.affiliation: Laboratory Medicine Program, Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, The University of Toronto, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Stockley
authors.affiliation: Laboratory Medicine Program, Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, The University of Toronto, Toronto, Ontario, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, The University Health Network, Toronto, Ontario, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics; D005821:Genetic Techniques; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000145:classification* / Q000235:genetics*; D010865:Pilot Projects