Medulloblastoma, macrocephaly, and a pathogenic germline PTEN variant: Cause or coincidence?

Abstract

Background Medulloblastomas (MBs) are a heterogeneous group of childhood brain tumors with four consensus subgroups, namely MBSHH, MBWNT, MBGroup 3, and MBGroup 4, representing the second most common type of pediatric brain cancer after high‐grade gliomas. They suffer from a high prevalence of genetic predisposition with up to 20% of MBSHH caused by germline mutations in only six genes. However, the spectrum of germline mutations in MBSHH remains incomplete. Methods Comprehensive Next‐Generation Sequencing panels of both tumor and patient blood samples were performed as molecular genetic characterization. The panels cover genes that are known to predispose to cancer. Results Here, we report on a patient with a pathogenic germline PTEN variant resulting in an early stop codon p.(Glu7Argfs*4) (ClinVar ID: 480383). The patient developed macrocephaly and MBSHH, but reached remission with current treatment protocols. Conclusions We propose that pathogenic PTEN variants may predispose to medulloblastoma, and show that remission was reached with current treatment protocols. The PTEN gene should be included in the genetic testing provided to patients who develop medulloblastoma at an early age. We recommend brain magnetic resonance imaging upon an unexpected acceleration of growth of head circumference for pediatric patients harboring pathogenic germline PTEN variants.

Cerebellar phenotypes in germline PTEN mutation carriers

“…PTEN-ASD patients manifested a greater severity of cognitive deficits in comparison with PTENwt ASD patients [15]. On the other hand, while the core ASD symptoms are similar in both PHTS and…”

“…PTEN ‐ASD patients manifested a greater severity of cognitive deficits in comparison with PTEN wt ASD patients [15]. On the other hand, while the core ASD symptoms are similar in both PHTS and PTEN wt ASD with concurrent macrocephaly, PTEN ‐correlated ASD showed lower clinical ratings of autism severity as well as more sensory abnormalities compared to the sporadic disorder.…”

“…Furthermore, rare cases of germline PTEN variants have been reported in patients with medulloblastoma, the most frequent cerebellar malignancy in childhood, but their role as a possible cause or predisposing factor has yet to be confirmed [15].…”

The Role of MicroRNAs in Therapeutic Resistance of Malignant Primary Brain Tumors

“…There is evidence that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) dysfunction plays a crucial role in the development and progression MB. PTEN plays important roles in many cellular processes, including cell-cycle progression and apoptosis (Tolonen et al, 2020). Li et al (2015) reported the upregulation of miR-106b in MB.…”

SHH medulloblastoma and very early onset of bowel polyps in a child with PTEN hamartoma tumor syndrome

“…Recently, it has been shown that the SHH subgroup is most frequently (approximately 20–40%) associated with germline mutations ( BRCA2 , PALB2 , PTCH1 , SUFU , and TP53 ; Waszak et al, 2018 ; Garcia-Lopez et al, 2021 ). Currently, MB cases are rarely described in individuals with Cowden syndrome ( Waszak et al, 2018 ; Tolonen et al, 2020 ), a condition included in the PHTS spectrum. Instead, cases associated with other CNS tumors such as dysplastic gangliocytoma, meningioma, pineal tumor, oligodendroglioma, and glioblastoma have been reported in patients with this condition ( Kim et al, 2020 ).…”