38. Formation of a tumor-specific gene list: The Central Nervous System (CNS) tumor taskforce experience

Modern molecular diagnostic tests allow detection of various genomic aberrations simultaneously. There are multiple recommendations to guide analysis of gene alterations in the somatic setting. However, resources for interpretation of tumor-type specific gene(s) are limited but are imperative for reliable and timely reporting of oncological molecular test results. Tumor-type specific gene lists enable the compilation of a comprehensive set of scrutinized genes with clinical implication. Our group extracted 670 genes from the TCGA CNS database, WHO Classification of CNS tumors and EANO guidelines. Gene-specific information including association with different tumor entities, type of alterations, mechanism of action, and hereditary risk if germline, were assessed. We applied the proposed framework for curation of cancer-specific gene lists created by collaborative effort of two Cancer Genomics Consortium Committees (Educational and GRDC) and modified the proposed criteria, including gene list creation and standardization. Each gene was reviewed independently by two reviewers who conducted literature searches for patient-based studies. We then assembled a detailed list of genes altered in CNS tumors and assessed their clinical relevance using categories of diagnostic, prognostic and therapeutic significance. Level of significance for each category was graded; 1 as 'recognized by guidelines', 2 as having 'supportive level of significance' in guidelines, and 3 as evidence of 'emerging data' for inclusion. Here we present the final list of 450 prioritized genes with specific criteria for assessment of significance pertaining to CNS tumors. Genes with insufficient evidence for inclusion were moved to a 'parking lot' list for future re-evaluation.