Data documento
02/05/2024

Título
High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population

Autor(es)
Moreno DA - Bonatelli M - Antoniazzi AP - de Paula FE - Leal LF - Garcia FAO - de Paula AE - Teixeira GR - Santana IVV - Saggioro F - Neder L - Valera ET - Scrideli CA - Stavale J - Malheiros SMF - Lima M - Hajj GNM - Garcia-Rivello H - Christiansen S - Nunes S - Gil-da-Costa MJ - Pinheiro J - Martins FD - Junior CA - Mançano BM - Reis RM.

Resumo
Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.

Citação
Moreno DA, Bonatelli M, Antoniazzi AP, de Paula FE, Leal LF, Garcia FAO, de Paula AE, Teixeira GR, Santana IVV, Saggioro F, Neder L, Valera ET, Scrideli CA, Stavale J, Malheiros SMF, Lima M, Hajj GNM, Garcia-Rivello H, Christiansen S, Nunes S, Gil-da-Costa MJ, Pinheiro J, Martins FD, Junior CA, Mançano BM, Reis RM. High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population. Front Oncol. 2023 Sep 4;13:1237170. doi: 10.3389/fonc.2023.1237170. PMID: 37746264; PMCID: PMC10513896.

Data documento
03/05/2024

Título
Somatic mutation detection and KRAS amplification in testicular germ cell tumors

Autor(es)
Cabral ERM, - Pacanhella MF, - Lengert AVH, - Dos Reis MB, - Leal LF, - de Lima MA, - da Silva ALV, - Pinto IA, - Reis RM, - Pinto MT, - Cárcano FM.

Palavras chave
K-ras Gene - TP53 Gene - mutation - next-generation sequencing - testicular germ cell tumor - testicular neoplasms

Resumo
Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

Citação
Cabral ERM, Pacanhella MF, Lengert AVH, Dos Reis MB, Leal LF, de Lima MA, da Silva ALV, Pinto IA, Reis RM, Pinto MT, Cárcano FM. Somatic mutation detection and KRAS amplification in testicular germ cell tumors. Front Oncol. 2023 Mar 16;13:1133363. doi: 10.3389/fonc.2023.1133363. PMID: 37007070; PMCID: PMC10060882.