Molecular profiling of colorectal pulmonary metastases and primary tumours: implications for targeted treatment
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Sing Y. Moorcraft1, Thomas Jones2, Brian A. Walker1, George Ladas2, Eleftheria Kalaitzaki1, Lina Yuan1, Ruwaida Begum1, Zakaria Eltahir1, Andrew Wotherspoon1, Angeles Montero-Fernandez2, Larissa S. Teixeira Mendes1, David Gonzalez de Castro1, Sanna Hulkki Wilson1, Paula Proszek1, Ye M. To1, Eliza Hawkes1, Amitesh Roy1, David Cunningham1, Sheela Rao1, David Watkins1, Naureen Starling1, Anne M. Bowcock3 and Ian Chau1
1The Royal Marsden NHS Foundation Trust, London and Sutton, United Kingdom
2The Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
3National Heart and Lung Institute, Imperial College, London, United Kingdom
Ian Chau, email: [email protected]
Keywords: colorectal cancer, heterogeneity, metastasectomy, pulmonary metastases, RAS
Received: October 06, 2016 Accepted: March 29, 2017 Published: April 11, 2017
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.
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