Genomic Features for Therapeutic Insights of Chemotherapy‐Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart. (18th January 2019)

• Record Type: Journal Article
• Authors: Necchi, Andrea; Bratslavsky, Gennady; Chung, Jon; Millis, Sherri; Gay, Laurie M.; Ali, Siraj M.; Ross, Jeffrey S.
• Is Part Of: Oncologist. Volume 24:Number 4(2019)
• Page Start: e142
• Page End: e145
• Publication Date: 2019-01-18
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2018-0430
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) frequently become refractory to chemotherapy, and no effective salvage therapy exists. We performed genomic profiling on a series of 44 PMNSGCT and compared the results with those from chemorefractory, metastatic pure seminomatous (Sem, n = 22) and nonseminomatous (NS, n = 86) testicular germ cell tumors. Archival tissues were sequenced by a hybrid capture‐based technology (FoundationONE; Foundation Medicine, Inc., Cambridge, MA). Microsatellite instability (MSI) and tumor mutational burden (TMB, mutations [mut]/Mb) were determined. Statistically significant differences in genomic alterations (GA) of PMNSGCT versus NS included higher TP53 pathway GA ( p < .0001), PIK3CA pathway GA ( p < .0001), and lower cell‐cycle pathway GA ( p = .0004). There were no MSI‐high PMNSGCT cases. Mean TMB was similar between the groups, but there were more ≥10 mut/Mb in the PMNSGCT group versus NS (11.4% vs. 4.6%). The GA identified in PMNSGCT were similar to the findings from NS, with differential opportunities for targeted therapies and immunotherapies. Further study of precision treatments appears warranted. Abstract : Primary mediastinal nonseminomatous (PMN) germ cell tumor are rare neoplasms arising from the anterior mediastinum in young adults. This article analyzes a large series of patients with germ cell tumors, including PMN germ cell tumors, and aims to identify precision treatments for this aggressive disease.