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

被引：2

作者：

Moreno, Daniel Antunes ^{[1
]}

Bonatelli, Murilo ^{[2
]}

Antoniazzi, Augusto Perazzolo ^{[3
]}

de Paula, Flavia Escremim ^{[2
]}

Leal, Leticia Ferro ^{[1
,5
]}

Garcia, Felipe Antonio de Oliveira ^{[1
]}

de Paula, Andre Escremim ^{[2
]}

Teixeira, Gustavo Ramos ^{[4
,5
]}

Santana, Iara Viana Vidigal ^{[4
]}

Saggioro, Fabiano ^{[6
]}

Neder, Luciano ^{[6
]}

Valera, Elvis Terci ^{[7
]}

Scrideli, Carlos Alberto ^{[7
]}

Stavale, Joao ^{[8
]}

Malheiros, Suzana Maria Fleury ^{[8
]}

Lima, Matheus ^{[9
]}

Hajj, Glaucia Noeli Maroso ^{[9
]}

Garcia-Rivello, Hernan ^{[10
]}

Christiansen, Silvia ^{[10
]}

Nunes, Susana ^{[11
]}

Gil-da-Costa, Maria Joao ^{[11
]}

Pinheiro, Jorge ^{[12
]}

Martins, Flavia Delgado ^{[13
]}

Almeida Junior, Carlos ^{[14
]}

Mancano, Bruna Minniti ^{[15
]}

Reis, Rui Manuel ^{[1
,2
,16
,17
]}

机构：

[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, Brazil

[2] Barretos Canc Hosp, Mol Diag Lab, Barretos, Brazil

[3] Barretos Canc Hosp, Canc Genet Dept, Barretos, Brazil

[4] Barretos Canc Hosp, Barretos Sch Hlth Sci Dr Paulo Prata, Barretos, Brazil

[5] Barretos Canc Hosp, Pathol Dept, Barretos, Brazil

[6] Univ Sao Paulo, Dept Pathol & Forens Med, Ribeirao Preto, Brazil

[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ribeirao Preto, Brazil

[8] Fed Univ Sao Paulo UNIFESP, Dept Neurol & Neurosurg, Sao Paulo, Brazil

[9] AC Camargo Hosp, Oncol Dept, Sao Paulo, Brazil

[10] Italian Hosp Buenos Aires, Pathol Dept, Buenos Aires, Argentina

[11] Univ Sao Joao, Pediat Oncol Dept, Ctr Hosp, Porto, Portugal

[12] Univ Sao Joao, Dept Pathol, Ctr Hosp, Porto, Portugal

[13] Brasilia Childrens Hosp, Brasilia, Brazil

[14] Barretos Canc Hosp, Pediat Neurosurg Dept, Barretos, Brazil

[15] Barretos Canc Hosp, Pediat Oncol Dept, Barretos, Brazil

[16] PT Govt Associate Lab, ICVS 3Bs, Guimaraes, Portugal

[17] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal

来源：

FRONTIERS IN ONCOLOGY | 2023年 / 13卷

关键词：

medulloblastomas; WNT activated; CTNNB1; APC; Latin-Iberian; FAMILIAL ADENOMATOUS POLYPOSIS; APC GERMLINE MUTATIONS; CENTRAL-NERVOUS-SYSTEM; CLASSIFICATION; INDIVIDUALS; DIVERSITY; CATENIN; TP53;

D O I：

10.3389/fonc.2023.1237170

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (similar to 30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

引用

页数：10