Analysis of the MOSAIC correlative cancer database integrating molecular cancer classification and tumor profiling to identify targeted treatment options for metastatic cancer.

Abstract

3121 Background: Unless tumor type and genetic alterations can be identified, metastatic cancer patients with unknown or uncertain diagnoses may be limited to empiric chemotherapy. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor types and subtypes for patients with cancer of unknown primary (CUP) or ambiguous diagnoses. Multimodal molecular biomarker testing by next-generation sequencing (NGS), tumor mutational burden (TMB), fluorescent in situ hybridization (FISH), microsatellite instability (MSI), and immunohistochemistry (IHC) can identify genetic targets. A database integrating tumor typing with biomarker analysis in metastatic cases was utilized to identify the most prevalent genetic alterations by tumor type. Methods: MOSAIC (Molecular Synergy to Advance Individualized Cancer Care) is an IRB-approved database of cases with CancerTYPE ID testing plus multimodal biomarker testing. The current study determined molecular tumor type followed by molecular profiling by NGS for up to 323 genes, (NeoTYPE profiles, Neogenomics). Results: Tumor type was determined in 1992 of 2151 cases (92.7%), comprised of 27 different tumor types. 72% of cases were comprised of the 7 tumor types shown in the table,which also shows the frequency of the 10 most commonly mutated genes by tumor type. Bolded are genes with actionable genetic mutations for which FDA-approved therapies are not currently indicated in the identified tumor type. Conclusions: Precise targeted treatment for many patients with CUP or ambiguous diagnoses requires accurate diagnosis of the cancer origin combined with multimodal molecular testing to identify actionable genetic alterations in the appropriate cellular context. Future studies will evaluate additional biomarker profiles, including TMB, FISH, MSI, and IHC for cases in the MOSAIC database.[Table: see text]