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ORIGINAL ARTICLE Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma A Retrospective Study Marco Lo Iacono, PhD,* Valentina Monica, PhD,* Luisella Righi, MD* Federica Grosso, MD,† Roberta Libener, MD,† Simona Vatrano, BS,* Paolo Bironzo, MD,* Silvia Novello, MD,* Loredana Musmeci, MD,‡ Marco Volante, MD,* Mauro Papotti, MD,* and Giorgio V. Scagliotti, MD* (TTPD p value = 0.02, overall survival p value = 0.04). BAP1 genetic Introduction: Malignant pleural mesothelioma (MPM) is a rare variations identified were mainly located in exons 13 and 17, and malignant disease, and the understanding of molecular pathogenesis BAP1 nonsynonymous variations were significantly correlated with has lagged behind other malignancies. BAP1 protein nuclear localization. Methods: A series of 123 formalin-fixed, paraffin-embedded tissue Conclusion: Next-generation sequencing was applied to a relatively samples with clinical annotations were retrospectively tested with a large retrospective series of MPM using formalin-fixed, paraffin- commercial library kit (Ion AmpliSeq Cancer Hotspot Panel v.2, Life embedded archival material. Our results indicate a complex muta- Technologies, Grand Island, NY) to investigate 50 genes plus other tional landscape with a higher number of genetic variations in the two, BRCA1-associated protein-1 (BAP-1) and neurofibromatosis-2 p53/DNA repair and phosphatidylinositol 3-kinase pathways, some (NF2), frequently altered in MPM. DNA was obtained from tissues of
Journal of Thoracic Oncology – Wolters Kluwer Health
Published: Mar 1, 2015
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