A National Platform For Molecular Diagnostics: Results Of The Cancer Research Uk Stratified Medicine Programme

11079 Background: Increasing demand for testing multiple markers for targeted therapies requires a platform to incorporate molecular diagnostics in the normal pathway of care. This programme was planned to demonstrate the applicability of a nationwide platform of testing, linked to healthcare records in a central database. Methods: From 8/2011 to 6/2013, patients with breast, colorectal, prostate, lung or ovarian cancer, or melanoma, were approached at 26 hospitals for consent to centralised molecular testing of routine biopsies. Formalin-fixed paraffin-embedded sections were forwarded with peripheral blood samples to 3 technical hubs for analysis of a small panel of abnormalities by Sanger sequencing, pyrosequencing or similar mathods, and fluorescent in-situ hybridisation for chromosomal structural changes. Results were transmitted directly to clinical centers for inclusion in medical records. A routine clinical dataset was collected from all patients using the national cancer registration system. Results: 10,754 patients (98% of those approached) consented to analysis of material, with 9010 samples sent for analysis. Of 1,889 lung cancers, 35% had at least one abnormality, only 0.65% had more than one. kRAS was most often mutated (26%), followed by EGFR (8.3%), Alk rearrangement (1.9%) and BRAF (1%). In 1634 colorectal cancers, 47% had one abnormality, 30% two and 3% three. Commonest abnormalities were mutated TP53 (25%), double mutated TP53 and kRAS ( 17%), kRAS only (17%) and BRAF (5%). In 535 melanomas there were 42% BRAF mutants, 22% NRAS mutant and only 2.4% with double abnormalities. There was heterogeneity between the laboratories in turnaround time and failure rate, especially for non-standard analyses. A multiplex next-generation sequencing (NGS) panel was piloted for samples collected in the last 3 months of the programme, showing high levels of concordance in comparison to conventional sequencing. Conclusions: A broad system of molecular diagnostics is feasible and highly acceptable to patients. The efficiency is improved with NGS analysis, and the system is now being used to support prescreening of patients with lung cancer for entry into a multiarm study of novel therapeutics.