: Sertoli cell tumor is a type of testicular sex cord-stromal tumor (TSCST) typically driven by gain-of-function CTNNB1 variants. Recently, molecular studies have identified TSCSTs (including Sertoli cell tumors) with loss-of-function APC variants, raising the possibility that germline APC alterations may predispose to TSCSTs. In this study, we evaluated 4 TSCSTs from 4 individual patients, including 3 APC -mutant neoplasms identified in prior studies (1 in a patient with familial adenomatous polyposis [FAP] and 2 in patients with unknown syndromic status) and 1 tumor of unknown mutational status diagnosed in a patient with known FAP. Three neoplasms were typical Sertoli cell tumors, and 1 was a malignant unclassified TSCT. All neoplasms exhibited diffuse nuclear beta-catenin expression. Non-neoplastic tissue could be obtained for DNA sequencing in the 3 Sertoli cell tumors. Comparative assessment of non-neoplastic and lesional tissue in these cases suggested that germline APC variants with subsequent inactivation of the gene (loss of heterozygosity) were the likely oncogenic driver of these Sertoli cell tumors. In the malignant unclassified TSCSTs, APC inactivation was also interpreted as the most likely driver event, and the germline origin of the variant was inferred using a recently published method. The results of this study suggest that pathogenic germline APC alterations (eg, FAP and variants thereof) may predispose to TSCSTs.

Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors / Siegmund, Stephanie; Ricci, Costantino; Kao, Chia-Sui; Sangoi, Ankur R; Mohanty, Sambit; Fletcher, Christopher D M; Colecchia, Maurizio; Acosta, Andres M. - In: THE AMERICAN JOURNAL OF SURGICAL PATHOLOGY. - ISSN 0147-5185. - ELETTRONICO. - 47:12(2023), pp. 1432-1437. [10.1097/PAS.0000000000002132]

Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors

Ricci, Costantino;
2023

Abstract

: Sertoli cell tumor is a type of testicular sex cord-stromal tumor (TSCST) typically driven by gain-of-function CTNNB1 variants. Recently, molecular studies have identified TSCSTs (including Sertoli cell tumors) with loss-of-function APC variants, raising the possibility that germline APC alterations may predispose to TSCSTs. In this study, we evaluated 4 TSCSTs from 4 individual patients, including 3 APC -mutant neoplasms identified in prior studies (1 in a patient with familial adenomatous polyposis [FAP] and 2 in patients with unknown syndromic status) and 1 tumor of unknown mutational status diagnosed in a patient with known FAP. Three neoplasms were typical Sertoli cell tumors, and 1 was a malignant unclassified TSCT. All neoplasms exhibited diffuse nuclear beta-catenin expression. Non-neoplastic tissue could be obtained for DNA sequencing in the 3 Sertoli cell tumors. Comparative assessment of non-neoplastic and lesional tissue in these cases suggested that germline APC variants with subsequent inactivation of the gene (loss of heterozygosity) were the likely oncogenic driver of these Sertoli cell tumors. In the malignant unclassified TSCSTs, APC inactivation was also interpreted as the most likely driver event, and the germline origin of the variant was inferred using a recently published method. The results of this study suggest that pathogenic germline APC alterations (eg, FAP and variants thereof) may predispose to TSCSTs.
2023
Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors / Siegmund, Stephanie; Ricci, Costantino; Kao, Chia-Sui; Sangoi, Ankur R; Mohanty, Sambit; Fletcher, Christopher D M; Colecchia, Maurizio; Acosta, Andres M. - In: THE AMERICAN JOURNAL OF SURGICAL PATHOLOGY. - ISSN 0147-5185. - ELETTRONICO. - 47:12(2023), pp. 1432-1437. [10.1097/PAS.0000000000002132]
Siegmund, Stephanie; Ricci, Costantino; Kao, Chia-Sui; Sangoi, Ankur R; Mohanty, Sambit; Fletcher, Christopher D M; Colecchia, Maurizio; Acosta, Andres M
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/950736
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact