DNA-mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): A catalogue of clinically relevant cancer mutations to enable genome-directed cancer therapy.

Yeh P, Chen H, Andrews J, Naser R, Pao W, Horn L.

Source

Hematology/Oncology, Vanderbilt University.

Abstract

Background: Tumor gene mutation status is becoming increasingly important in the treatment of cancer patients. A comprehensive catalogue of tumor gene-response outcomes from individual patients is needed, especially for actionable mutations and rare variants. We created a proof-of-principle database (DNA-mutation Inventory to Refine and Enhance Cancer Treatment; (DIRECT)), starting with lung cancer-associated epidermal growth factor receptor (EGFR) mutations, to provide a resource for clinicians to prioritize treatment decisions based on a patient's tumor mutations at the point of care.¬ Methods: A systematic search of literature published between June 2005 and May 2011 was conducted through PubMed to identify patient-level, mutation-drug response in non-small cell lung cancer (NSCLC) patients with EGFR mutant tumors. Minimum inclusion criteria included patient's EGFR mutation, corresponding treatment, and an associated radiographic outcome. RESULTS: 1021 patients with 1070 separate EGFR TKI therapy-responses from 116 different publications were included. 188 unique EGFR mutations occurring in 207 different combinations were identified: 149 different mutation combinations were associated with disease control, and 42 were associated with disease progression. 4 secondary mutations, in 16 different combinations, were associated with acquired resistance. CONCLUSIONS: As tumor sequencing becomes more common in oncology, this comprehensive electronic catalogue can enable genome-directed anti-cancer therapy. DIRECT will eventually encompass all tumor mutations associated with clinical outcomes on targeted therapies. Users can make specific queries at http://mycancergenome.org/direct.php to obtain clinically relevant data associated with various mutations.