Molecular correlates of male germ cell tumors with overgrowth of components resembling somatic malignancies.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
05
05
2022
accepted:
22
06
2022
revised:
17
06
2022
pubmed:
28
8
2022
medline:
2
12
2022
entrez:
27
8
2022
Statut:
ppublish
Résumé
A small subset of male germ cell tumors (GCT) demonstrates overgrowth of histologic components that resemble somatic malignancies (e.g., sarcoma, carcinoma). The presence of so-called "somatic-type" malignancies (SM) in GCT has been associated with chemotherapy-resistance and poor clinical outcomes in prior studies. However, the molecular characteristics of these tumors remain largely undescribed. In this study, we performed a multi-platform molecular analysis of GCTs with SM diagnosed in 36 male patients (primary site: testis, 29 and mediastinum, 7). The most common histologic types of SM were sarcoma and embryonic-type neuroectodermal tumor (ENT, formerly known as "PNET"), present in 61% and 31% of cases, respectively. KRAS and TP53 mutations were identified by DNA sequencing in 28% of cases each, with enrichment of TP53 mutations in mediastinal tumors (86%). Gains in the short arm of chromosome 12 were seen in 91% of cases, likely reflecting the presence of isochromosome 12p. Numerous copy number changes indicative of widespread aneuploidy were found in 94% of cases. Focal homozygous deletions and amplifications were also detected, including MDM2 amplifications in 16% of cases. Sequencing of paired samples in 8 patients revealed similar mutational and copy number profiles in the conventional GCT and SM components. Oncogenic gene fusions were not detected using RNA sequencing of SM components from 9 cases. DNA methylation analysis highlighted the distinct methylation profile of SM components that sets them apart from conventional GCT components. In conclusion, GCT with SM are characterized by widespread aneuploidy, a distinct epigenetic signature and the presence of mutations that are otherwise rare in testicular GCT without SM. The similarity of the mutational and DNA methylation profiles of different histologic types of SM suggests that the identification of SM components could be more important than their precise histologic subclassification, pending confirmation by further studies.
Identifiants
pubmed: 36030288
doi: 10.1038/s41379-022-01136-1
pii: S0893-3952(22)05508-9
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1966-1973Informations de copyright
© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
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