TY - JOUR
T1 - Molecular profiling of colorectal pulmonary metastases and primary tumours: Implications for targeted treatment
AU - Moorcraft, Sing
AU - Jones, Thomas
AU - Walker, Brian
AU - Ladas, George
AU - Kalaitzaki, Eleftheria
AU - Yuan, Lina
AU - Begum, Ruwaida
AU - Eltahir, Zak
AU - Wotherspoon, Andrew
AU - Montero-Fernandez, Angeles
AU - Teixeira Mendes, Larissa
AU - Gonzalez de Castro, David
AU - Wilson, Sanna
AU - Proszek, Paula
AU - To, Ye
AU - Hawkes, Eliza
AU - Roy, Amitesh
AU - Cunningham, David
AU - Rao, Sheela
AU - Watkins, David
AU - Starling, Naureen
AU - Bowcock, Anne
AU - Chau, Ian
PY - 2017/4/11
Y1 - 2017/4/11
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - Heterogeneity
KW - Metastasectomy
KW - Pulmonary metastases
KW - RAS
UR - http://www.scopus.com/inward/record.url?scp=85030105845&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.17048
DO - 10.18632/oncotarget.17048
M3 - Article
VL - 8
SP - 64999
EP - 65008
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 39
ER -