Oncotarget

Research Papers:

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

Sing Y. Moorcraft, Thomas Jones, Brian A. Walker, George Ladas, Eleftheria Kalaitzaki, Lina Yuan, Ruwaida Begum, Zakaria Eltahir, Andrew Wotherspoon, Angeles Montero-Fernandez, Larissa S. Teixeira Mendes, David Gonzalez de Castro, Sanna Hulkki Wilson, Paula Proszek, Ye M. To, Eliza Hawkes, Amitesh Roy, David Cunningham, Sheela Rao, David Watkins, Naureen Starling, Anne M. Bowcock, Ian Chau _

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Abstract

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

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.

Author Information

Sing Y. Moorcraft

Thomas Jones

Brian A. Walker

George Ladas

Eleftheria Kalaitzaki

Lina Yuan

Ruwaida Begum

Zakaria Eltahir

Andrew Wotherspoon

Angeles Montero-Fernandez

Larissa S. Teixeira Mendes

David Gonzalez de Castro

Sanna Hulkki Wilson

Paula Proszek

Ye M. To

Eliza Hawkes

Amitesh Roy

David Cunningham

Sheela Rao

David Watkins

Naureen Starling

Anne M. Bowcock

Ian Chau
Primary Contact  _


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