Molecular profiling of colorectal pulmonary metastases and primary tumours: implications for targeted treatment

// Sing Y. Moorcraft 1 , Thomas Jones 2 , Brian A. Walker 1 , George Ladas 2 , Eleftheria Kalaitzaki 1 , Lina Yuan 1 , Ruwaida Begum 1 , Zakaria Eltahir 1 , Andrew Wotherspoon 1 , Angeles Montero-Fernandez 2 , Larissa S. Teixeira Mendes 1 , David Gonzalez de Castro 1 , Sanna Hulkki Wilson 1 , Paula Proszek 1 , Ye M. To 1 , Eliza Hawkes 1 , Amitesh Roy 1 , David Cunningham 1 , Sheela Rao 1 , David Watkins 1 , Naureen Starling 1 , Anne M. Bowcock 3 and Ian Chau 1 1 The Royal Marsden NHS Foundation Trust, London and Sutton, United Kingdom 2 The Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom 3 National Heart and Lung Institute, Imperial College, London, United Kingdom Correspondence to: Ian Chau, email: ian.chau@rmh.nhs.uk Keywords: colorectal cancer, heterogeneity, metastasectomy, pulmonary metastases, RAS Received: October 06, 2016      Accepted: March 29, 2017      Published: April 11, 2017 ABSTRACT This study aimed to molecularly characterise colorectal pulmonary metastases (PM) and investigate whether their molecular profiles were concordant with those of the primary tumour. Clinical data and archival formalin fixed paraffin embedded tissue samples were retrospectively collected from patients who underwent ≥ 1 pulmonary metastasectomies for colorectal cancer between 1997–2012. Primary tumour and metastatic samples were analysed using a targeted capture sequencing panel of 46 cancer-associated genes. The 5-year progression-free and overall survival rates for the 81 patients in this study were 32% (95% CI 22–42%) and 77% (95% CI 66–85%) respectively. Fifty-four patients had samples available from ≥ 1 PM, and sequencing data were successfully obtained from 33 PM from 24 patients. The most frequently mutated genes were APC (71%), KRAS (58%) and TP53 (46%). Seventy-three percent of the 15 patients with matched primary and PM samples and 6 of the 7 patients (86%) with data from ≥ 2 PM had concordant molecular profiles. The concordance for KRAS and NRAS was 100%. At our institutions, patients with resectable colorectal PM had a favourable prognosis. RAS mutations were commonly detected in PM and the molecular profiles of colorectal PM were highly concordant with the primary tumour.