Journal article

Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer

Tracy L Leong, Velimir Gayevskiy, Daniel P Steinfort, Marc R De Massy, Alvaro Gonzalez-Rajal, Kieren D Marini, Emily Stone, Venessa Chin, Adrian Havryk, Marshall Plit, Louis B Irving, Barton R Jennings, Rachael A McCloy, W Samantha N Jayasekara, Muhammad Alamgeer, Vishal Boolell, Andrew Field, Prudence A Russell, Beena Kumar, Daniel J Gough Show all

ONCOGENE | NATURE PUBLISHING GROUP | Published : 2019

Abstract

Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting..

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Grants

Awarded by Victorian Cancer Agency


Awarded by NHMRC Career Development Fellowship


Awarded by Victoria Cancer Agency Mid-Career Fellowship


Awarded by Cancer Institute NSW Early Career Fellowship


Awarded by NHMRC Senior Research Fellowship


Funding Acknowledgements

This work was supported by the Victorian Cancer Agency, (TS10-01), the Petre Foundation, the Victorian Government's Operational Infrastructure Support Program, the Baxter Charitable Foundation, the St Vincent's Clinic Foundation, Tour de Cure, the Australian Government NHMRC IRIISS, the Victorian State Government Operational Infrastructure Support, the Australian Cancer Therapeutics CRC (TLL), the Australian Cancer Research Foundation, an NHMRC Career Development Fellowship (GNT1063914, DJG), a Victoria Cancer Agency Mid-Career Fellowship (MCRF17014, JEC), a Viertel Foundation Senior Medical Researcher Fellowship (M-LA-L), a Cancer Institute NSW Early Career Fellowship (13ECF/1-46) and NSW Health Early-Mid-Career Fellowship (MJC), the Kinghorn Foundation (MJC, VG), and an NHMRC Senior Research Fellowship (GNT546107, DNW). We thank the Victorian Cancer Biobank for technical support.