Open AccessMedulloblastoma, macrocephaly, and a pathogenic germline PTEN variant: Cause or coincidence?
Author(s) -
Tolonen JussiPekka,
Hekkala Anne,
Kuismin Outi,
Tuominen Hannu,
SuoPalosaari Maria,
Tynninen Olli,
Niinimäki Riitta
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1302
Subject(s) - pten , macrocephaly , medulloblastoma , germline , germline mutation , cancer , cancer research , medicine , genetics , genetic testing , biology , oncology , gene , mutation , pi3k/akt/mtor pathway , apoptosis
Background Medulloblastomas (MBs) are a heterogeneous group of childhood brain tumors with four consensus subgroups, namely MB SHH , MB WNT , MB Group 3 , and MB Group 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 MB SHH caused by germline mutations in only six genes. However, the spectrum of germline mutations in MB SHH 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 MB SHH , 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.