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

PURPOSE

Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the gene (85%-90%), and most remaining cases wild type are thought to be caused by germline mutations in . So far, the frequencies of have been reported mainly in North American and European populations. The aim of this study was to report the frequency of 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 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 mutations. wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring germline variants.

CONCLUSION

We observed a lower incidence of mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that wild-type cases may exhibit germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.