Abstract
Primary sarcomas of the thorax are rare, which may arise in the lung, mediastinum, pleura and chest wall. Studies of comprehensive molecular characteristics and targeted therapy opportunity in thoracic sarcoma patients are lacking. Formalin fixed, paraffin embedded (FFPE) tumor tissues and matched blood samples of 30 thoracic sarcoma patients were collected for 450 cancer gene targeted next-generation sequencing (NGS) assay in a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations and tumor mutational burden (TMB) values were assessed by next-generation sequencing assay with a mean coverage of 1000X, including single base substitution, short and long insertion/deletions, copy number variations, gene fusions and rearrangements. In total, tumor samples from 30 thoracic sarcoma patients were recruited, including 16 males and 14 females with a median age of 39 (range 11-67). This cohort of patient was comprised of seven undifferentiated pleomorphic sarcoma (UPS), four spindle cell sarcoma, three inflammatory myofibroblastic tumor (IMTs), three Ewing sarcoma (ES), three myxofibrosarcoma, two pulmonary artery sarcoma, two rhabdomyosarcoma, two fibrosarcoma, two angiosarcoma, one leiomyosarcoma and one epithelioid sarcoma. The most frequently mutated genes were TP53 (33%), ATRX (27%), CDKN2A (17%), NF1 (17%), PDGFRA (17%), CCND3 (13%) and CDKN2B (13%). Cases with TP53 alterations had lower age than wild type TP53 (35 vs. 62 years, respectively, P=0.0035). The median TMB of total patients was 1.5 muts/Mb. Twelve (40%) patients harbored at least one actionable genomic alteration, including ALK, PDGFB, ROS1 rearrangement, VEGFA, PDGFRA, KDR,KIT, FGFR1, FGFR3, CDK4 amplification and CDKN2A,CDKN2B deletion. Here, we identified two patients with pulmonary IMT harboring TFG-ROS1 fusion, who achieved continuous remission following treatment with crizotinib (Figure 1). Our study revealed that approximately 40% of patients with thoracic sarcoma harbored at least one druggable genomic alteration. A broader molecular testing, such as NGS, is necessary to explore the comprehensive genetic characteristics and potential drug targets for patients with thoracic sarcoma.
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