Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study

Moreno, Daniel Antunes; Silva, Luciane Sussuchi da; Zanon, Maicon Fernando; Bonatelli, Murilo; Paula, Flávia Escremim de; Matsushita, Marcus de Medeiros; Teixeira, Gustavo Ramos; Santana, Iara Viana Vidigal; Saggioro, Fabiano Pinto; Neder, Luciano; Stávale, João Norberto; Malheiros, Suzana Mária Fleury; Lima, Matheus Henrique Alves De; Hajj, Glaucia Noeli Maroso; García‐Rivello, Hernán; Christiansen, Stefan; Nunes, Susana; Costa, Maria Joao Gil da; Soares, M. A.; Pinheiro, Jorge; Almeida, Carlos; Mançano, Bruna Minniti; Reis, Rui Manuel

doi:10.1007/s11060-022-03965-1

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…The DNA quantification was performed using the NanoDropVR 2000 (Thermo Fisher Scientific, Waltham, USA) ( 12 ). The RNA isolation was performed using the deparaffinization solution (Qiagen, Venlo, The Netherlands) and the RNeasy Mini Kit (Qiagen, Venlo, The Netherlands), and the Qubit 2.0 Fluorometer (RNA HS Assay kit, Life Technologies, Thermo Fisher Scientific, Waltham, USA) was applied for RNA quantification following the manufacturer’s recommendations ( 13 , 14 ).…”

Section: Methodsmentioning

confidence: 99%

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

Moreno,

Bonatelli,

Antoniazzi

et al. 2023

Front. Oncol.

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PurposeMedulloblastomas 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.MethodsA total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively.ResultsWNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants.ConclusionWe observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

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Section: Methodsmentioning

confidence: 99%

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

Moreno,

Bonatelli,

Antoniazzi

et al. 2023

Front. Oncol.

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“…We included 88 formalin-fixed paraffin-embedded (FFPE) medulloblastoma specimens from patients diagnosed at Barretos Cancer Hospital (BCH), Barretos, and Ribeirão Preto Medical School, Brazil, from 1986 to 2018. Experienced pathologists reviewed the histology, and the tumors were previously molecularly characterized by a 22-gene nCounter assay into WNT (n=14), SHH (n=43), Group 3 (n=12), and Group 4 (n=19) ( 5 , 18 , 19 ). This study was approved by the Ethics Committee in Research from Barretos’ Cancer Hospital (Project #1248/2016).…”

Section: Methodsmentioning

confidence: 99%

Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets

et al. 2023

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IntroductionMedulloblastoma is the most common and lethal pediatric malignant brain tumor. It comprises four main molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4. Medulloblastoma treatment is surgical resection, craniospinal radiation, and chemotherapy. However, many patients do not respond to therapy, and most suffer severe side effects. Cancer immunotherapy targeting immune checkpoints (IC) (PD-1, PD-L1, and CTLA4) has been getting disappointing outcomes in brain tumors. Nevertheless, other less explored immune checkpoints may be promising candidates for medulloblastoma therapy.ObjectivesIn the present study, we aimed to characterize the expression profile of 19 immune checkpoints in medulloblastoma.MethodsWe analyzed 88 formalin-fixed paraffin-embedded medulloblastomas previously classified for each molecular subgroup and three non-tumoral brain tissue. mRNA levels of 19 immune checkpoint-related genes were quantified using the nCounter (PanCancer Immune Profiling Panel) assay. Further in silico analysis was performed in two larger public microarray datasets, one of which enabled comparisons between tumoral and non-tumoral tissues. Immunohistochemistry of PD-L1 was performed in a subset of cases. Microsatellite instability was also molecularly analyzed.ResultsWe observed an absence of expression of the canonic ICs, namely PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, as well as CD80, CD86, BTLA, IDO1, CD48, TNFSF14, CD160, CEACAM1, and CD244. PD-L1 protein expression was also practically absent. We found higher mRNA levels of CD24, CD47, CD276 (B7-H3), and PVR, and lower mRNA levels of HAVCR2, LAG3, and TIGIT genes, with significant differences across the four molecular subgroups. Compared to the non-tumor tissues, the expression levels of CD276 in all subgroups and CD24 in SHH, Group 3, and Group 4 subgroups are significantly higher. The in silico analysis confirmed the expression profile found in the Brazilian cohort, including the lower/absent expression of the canonic ICs. Moreover, it confirmed the overexpression of CD24 and CD276 in medulloblastomas compared with the non-tumor tissue. Additionally, CD276 and CD24 high levels were associated with worse survival.ConclusionThese results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of CD24 and CD276, which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.

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“…Another major area of translational research for cancer patients has been molecular analysis and genetic testing, which enable scientists to identify the genomic vulnerabilities of tumors, understand tumor evolution, discover mechanisms of resistance and develop individualized therapies (11). In Latin America, traditionally these studies have been limited by economic constraints and a lack of investment in translational and clinical research; however, during the past decade, advances in these areas have been noted and should be reviewed to promote treatment tailored to individual needs (12)(13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America

Cancela,

Dinardi,

Aschero

et al. 2024

Revista Panamericana De Salud Pública

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Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

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Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study

Cited by 4 publications

References 33 publications

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

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

Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America

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