P1.04 Clinical Diagnostic Implementation of an Innovative Cancer Care Model Based on Comprehensive Molecular Profiling of Tumour-Normal Pairs

Abstract

Molecular profiling of cancer samples within clinical diagnostics laboratories can have strong predictive value for patient prognosis, the development of drug resistance and can inform the selection of appropriate therapeutic options. The number of genes with a proven cancer therapeutic value has increased greatly in recent years however, in UK clinical diagnostics, routine molecular profiling of tumours for somatic mutations is confined to a very limited selection of genes. Comprehensive screening of multiple genes in parallel is likely to increase the impact of molecular profiling for clinical use by identifying the mutations that may influence response to therapy, tumour progression and the development of drug resistance, for each individual patient. As part of a Technology Strategy Board funded large scale academia-industry collaboration in partnership with Life-Technologies, Astra Zeneca and Johnson & Johnson, we have initiated a clinical study to implement an innovative cancer care model using a next generation sequencing based diagnostic test that provides a comprehensive molecular profile by screening tumour-normal pairs for mutations in a 150 gene panel. Concomitant software development will convert sequence data to annotated mutations and provide clinical decision support. As a precursor to this test, we have evaluated the workflow, bioinformatics pipeline and accuracy of Ion AmpliSeq(TM) Cancer HotSpot Panel targeted enrichment and Ion Torrent PGM(TM) sequencing for routine use in a clinical molecular diagnostics environment as a method for introducing a molecular profiling strategy for clinical diagnostic use. We screened a cohort of forty formalin fixed paraffin embedded samples with 54 known clinically relevant mutations identified by di-deoxy sequencing in six genes. We identified 52 of the positive control mutations (>95% sensitivity) and developed an early stage pipeline for moving from sequence data to clinical relevance. 33 mutations of probable clinical interest were identified in addition to the positive controls; a subset of these mutations is being investigated further in the research laboratory. The assay is currently being translated to the Oxford University Hospital NHS Trust molecular diagnostics laboratory, where it is being implemented alongside existing molecular diagnostic testing methods.