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Genomic Features for Therapeutic Insights of Chemotherapy-Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart.
- Source :
-
The oncologist [Oncologist] 2019 Apr; Vol. 24 (4), pp. e142-e145. Date of Electronic Publication: 2019 Jan 18. - Publication Year :
- 2019
-
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.<br />Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article.<br /> (© AlphaMed Press 2019.)
- Subjects :
- Adult
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Male
Mediastinal Neoplasms pathology
Neoplasms, Germ Cell and Embryonal pathology
Neoplasms, Germ Cell and Embryonal secondary
Prognosis
Signal Transduction
Testicular Neoplasms pathology
Testicular Neoplasms secondary
Biomarkers, Tumor genetics
Drug Resistance, Neoplasm genetics
Genomics methods
Mediastinal Neoplasms genetics
Mutation
Neoplasms, Germ Cell and Embryonal genetics
Testicular Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1549-490X
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The oncologist
- Publication Type :
- Academic Journal
- Accession number :
- 30659078
- Full Text :
- https://doi.org/10.1634/theoncologist.2018-0430