Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.

Autor:	Oey H; Diamantina Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Australia., Daniels M; Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Queensland, Australia., Relan V; Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Queensland, Australia., Chee TM; Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Queensland, Australia., Davidson MR; Department of Anatomical Pathology, The Prince Charles Hospital, Queensland, Australia., Yang IA; Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Queensland, Australia.; Department of Thoracic Medicine, The Prince Charles Hospital, Queensland, Australia., Ellis JJ; Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology (QUT) at Translational Research Institute, Brisbane, Australia., Fong KM; Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Queensland, Australia.; Department of Thoracic Medicine, The Prince Charles Hospital, Queensland, Australia., Krause L; Diamantina Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Australia., Bowman RV; Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Queensland, Australia.; Department of Thoracic Medicine, The Prince Charles Hospital, Queensland, Australia.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2019 Jul 06; Vol. 40 (6), pp. 724-734.
DOI:	10.1093/carcin/bgz066
Abstrakt:	Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes. (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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