دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population.
المؤلفون: Moreno DA; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Bonatelli M; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, Brazil., Antoniazzi AP; Cancer Genetics Department, Barretos Cancer Hospital, Barretos, Brazil., de Paula FE; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, Brazil., Leal LF; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Pathology Department, Barretos Cancer Hospital, Barretos, Brazil., Garcia FAO; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., de Paula AE; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, Brazil., Teixeira GR; Barretos School of Health Sciences Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil.; Pathology Department, Barretos Cancer Hospital, Barretos, Brazil., Santana IVV; Barretos School of Health Sciences Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., Saggioro F; Department of Pathology and Forensic Medicine, University of São Paulo, Ribeirão Preto, Brazil., Neder L; Department of Pathology and Forensic Medicine, University of São Paulo, Ribeirão Preto, Brazil., Valera ET; Department of Pediatrics of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Scrideli CA; Department of Pediatrics of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Stavale J; Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, Brazil., Malheiros SMF; Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, Brazil., Lima M; Oncology Department, AC Camargo Hospital, São Paulo, Brazil., Hajj GNM; Oncology Department, AC Camargo Hospital, São Paulo, Brazil., Garcia-Rivello H; Pathology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina., Christiansen S; Pathology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina., Nunes S; Pediatric Oncology Department, Centro Hospitalar Universitário São João, Porto, Portugal., Gil-da-Costa MJ; Pediatric Oncology Department, Centro Hospitalar Universitário São João, Porto, Portugal., Pinheiro J; Department of Pathology, Centro Hospitalar Universitário São João, Porto, Portugal., Martins FD; Brasília Children's Hospital, Brasília, Brazil., Junior CA; Pediatric Neurosurgery Department, Barretos Cancer Hospital, Barretos, Brazil., Mançano BM; Pediatric Oncology Department, Barretos Cancer Hospital, Barretos, Brazil., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Molecular Diagnosis Laboratory, Barretos Cancer Hospital, Barretos, Brazil.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
المصدر: Frontiers in oncology [Front Oncol] 2023 Sep 04; Vol. 13, pp. 1237170. Date of Electronic Publication: 2023 Sep 04 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مستخلص: Purpose: 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.
Methods: A 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.
Results: WNT-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.
Conclusion: We 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Moreno, Bonatelli, Antoniazzi, de Paula, Leal, Garcia, de Paula, Teixeira, Santana, Saggioro, Neder, Valera, Scrideli, Stavale, Malheiros, Lima, Hajj, Garcia-Rivello, Christiansen, Nunes, Gil-da-Costa, Pinheiro, Martins, Junior, Mançano and Reis.)
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فهرسة مساهمة: Keywords: APC; CTNNB1; Latin-Iberian; WNT activated; medulloblastomas
تواريخ الأحداث: Date Created: 20230925 Latest Revision: 20230926
رمز التحديث: 20230926
مُعرف محوري في PubMed: PMC10513896
DOI: 10.3389/fonc.2023.1237170
PMID: 37746264
قاعدة البيانات: MEDLINE
الوصف
تدمد:2234-943X
DOI:10.3389/fonc.2023.1237170