Available Resources and Challenges for the Clinical Annotation of Somatic Variations

Next-generation sequencing (NGS) has become an important tool for identifying clinically relevant variants in both inherited disorders and oncology. Variants annotation that enables the creation of meaningful clinical reports often requires mining multiple publicly available databases. There are a number of such resources that have been designed to catalog and mine a plethora of germline variants or mutations. However, when analyzing tumor specimens in clinical settings, one may need to use different or ancillary resources that are specific for somatic variants or actionable mutations that may have clinical or treatment implications. The purpose of this review is to recapitulate the state of the art of somatic variation databases, which can aid in the clinical interpretation of NGS-based assays in oncology. In addition, the current need for collating various annotation sources into one-stop solutions to facilitate faster query execution and better integration into existing laboratory information systems are discussed. Cancer (Cancer Cytopathol) 2014;122:730-736. (c) 2014 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This review focuses on the publicly available resources for the annotation of somatic variants found by next-generation sequencing (NGS) technologies applied to mutational analyses of tumor specimens in clinical settings. The characteristics of the existing databases as well as the ideal tools needed to comprehensively annotate mutations for the creation of clinically relevant reports for oncology are discussed.