Open AccessGenomic Features for Therapeutic Insights of Chemotherapy‐Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart
Author(s) -
Necchi Andrea,
Bratslavsky Gennady,
Chung Jon,
Millis Sherri,
Gay Laurie M.,
Ali Siraj M.,
Ross Jeffrey S.
Publication year - 2019
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2018-0430
Subject(s) - medicine , germ cell tumors , chemotherapy , germ cell , oncology , cancer research , gene , genetics , biology
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.