期刊
MODERN PATHOLOGY
卷 36, 期 7, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.modpat.2023.100152
关键词
non germ cell tumor; Sertoli cell tumor; sex cord-stromal tumor; testicular cancer; testis
类别
This study analyzed a series of non-metastasizing and metastasizing SCTs using next-generation DNA sequencing and found that non-metastasizing SCTs were mainly driven by CTNNB1 and APC gene variants, while metastasizing SCTs were mainly caused by variants in TP53, MDM2, CDKN2A/CDKN2B, and TERT genes.
Sertoli cell tumor (SCT) is the second most common type of sex cord-stromal tumor in men, and-10% exhibit malignant behavior. Although CTNNB1 variants have been described in SCTs, only a limited number of metastatic cases have been analyzed, and the molecular alterations associated with aggressive behavior remain largely unexplored. This study evaluated a series of non-metastasizing and metastasizing SCTs using next-generation DNA sequencing to further characterize their genomic landscape. Twenty-two tumors from 21 patients were analyzed. Cases were divided into metastasizing SCTs and nonmetastasizing SCTs. Nonmetastasizing tumors were considered to have aggressive histopathologic features if they exhibited >1 of the following: size > 2.4 cm, ne-crosis, lymphovascular invasion, >3 mitoses per 10 high-power fields, severe nuclear atypia, or invasive growth. Six patients had metastasizing SCTs, and the remaining 15 patients had non-metastasizing SCTs; 5 nonmetastasizing tumors had >1 aggressive histopathologic feature(s). Gain-of-function CTNNB1 or inactivating APC variants were highly recurrent in nonmetastasizing SCTs (combined frequency >90%), with arm-level/chromosome-level copy number variants, loss of 1p, and CTNNB1 loss of heterozygosity occurring exclusively in CTNNB1-mutant tumors with aggressive histopathologic features or size >1.5 cm. Nonmetastasizing SCTs were almost invariably driven by WNT pathway activation. In contrast, only 50% of metastasizing SCTs harbored gain-of-function CTNNB1 variants. The remaining 50% of metastasizing SCTs were CTNNB1-wild-type and harbored alterations in the TP53, MDM2, CDKN2A/CDKN2B, and TERT pathways. These findings suggest that-50% of aggressive SCTs represent progression of CTNNB1-mutant benign SCTs, whereas the remaining ones are CTNNB1-wild-type neoplasms that exhibit alterations in genes of the TP53, cell cycle regulation, and telomere maintenance pathways.(c) 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.
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