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Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.
Creaney, Jenette; Patch, Ann-Marie; Addala, Venkateswar; Sneddon, Sophie A; Nones, Katia; Dick, Ian M; Lee, Y C Gary; Newell, Felicity; Rouse, Ebony J; Naeini, Marjan M; Kondrashova, Olga; Lakis, Vanessa; Nakas, Apostolos; Waller, David; Sharkey, Annabel; Mukhopadhyay, Pamela; Kazakoff, Stephen H; Koufariotis, Lambros T; Davidson, Aimee L; Ramarao-Milne, Priya; Holmes, Oliver; Xu, Qinying; Leonard, Conrad; Wood, Scott; Grimmond, Sean M; Bueno, Raphael; Fennell, Dean A; Pearson, John V; Robinson, Bruce W; Waddell, Nicola.
Afiliação
  • Creaney J; National Centre for Asbestos Related Disease, Medical School, University of Western Australia, Level 5, QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA, 6009, Australia.
  • Patch AM; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
  • Addala V; Centre for Respiratory Health, University of Western Australia, Nedlands, WA, Australia.
  • Sneddon SA; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Nones K; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
  • Dick IM; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Lee YCG; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
  • Newell F; National Centre for Asbestos Related Disease, Medical School, University of Western Australia, Level 5, QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA, 6009, Australia.
  • Rouse EJ; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Naeini MM; National Centre for Asbestos Related Disease, Medical School, University of Western Australia, Level 5, QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA, 6009, Australia.
  • Kondrashova O; Centre for Respiratory Health, University of Western Australia, Nedlands, WA, Australia.
  • Lakis V; National Centre for Asbestos Related Disease, Medical School, University of Western Australia, Level 5, QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA, 6009, Australia.
  • Nakas A; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
  • Waller D; Centre for Respiratory Health, University of Western Australia, Nedlands, WA, Australia.
  • Sharkey A; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Mukhopadhyay P; National Centre for Asbestos Related Disease, Medical School, University of Western Australia, Level 5, QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA, 6009, Australia.
  • Kazakoff SH; Centre for Respiratory Health, University of Western Australia, Nedlands, WA, Australia.
  • Koufariotis LT; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Davidson AL; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Ramarao-Milne P; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Holmes O; Cancer Research UK Centre Leicester, University of Leicester & University Hospitals of Leicester NHS Trust, Leicester, UK.
  • Xu Q; Cancer Research UK Centre Leicester, University of Leicester & University Hospitals of Leicester NHS Trust, Leicester, UK.
  • Leonard C; Cancer Research UK Centre Leicester, University of Leicester & University Hospitals of Leicester NHS Trust, Leicester, UK.
  • Wood S; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Grimmond SM; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Bueno R; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Fennell DA; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Pearson JV; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
  • Robinson BW; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Waddell N; Medical Genomics, Clinical Genomics and Genome Informatics Groups, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Genome Med ; 14(1): 58, 2022 05 30.
Article em En | MEDLINE | ID: mdl-35637530
ABSTRACT

BACKGROUND:

Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.

METHODS:

We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study. This was combined with RNA-seq analysis to characterize the tumour immune environment.

RESULTS:

The comprehensive genome analysis identified 12 driver genes, including new candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed SBS5/40 were dominant in 93% of samples, and defects in homologous recombination repair were infrequent in our cohort. The tumour immune environment contained high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immune suppressive environment. The expression of TGFB1 was associated with overall survival. A small subset of samples (less than 10%) had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a 'hot' immune environment independent of the somatic mutations.

CONCLUSIONS:

We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pleurais / Mesotelioma Maligno / Neoplasias Pulmonares / Mesotelioma Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pleurais / Mesotelioma Maligno / Neoplasias Pulmonares / Mesotelioma Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article