ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma.

Purpose: Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established.

Experimental Design: We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations.

Results: ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0-80 years).

Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.

We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53) but showed alterations in TP53 pathway members PPM1D and MDM4.

Liquid biopsy detection of genomic alterations in pediatric brain tumors from cell-free DNA in peripheral blood, CSF, and urine.

Background: The ability to identify genetic alterations in cancers is essential for precision medicine; however, surgical approaches to obtain brain tumor tissue are invasive. Profiling circulating tumor DNA (ctDNA) in liquid biopsies has emerged as a promising approach to avoid invasive procedures. Here, we systematically evaluated the feasibility of profiling pediatric brain tumors using ctDNA obtained from plasma, cerebrospinal fluid (CSF), and urine.

A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes.

Background: Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically based therapies for this tumor are therefore desperately needed.

Novel predictive scoring system for morbid hypothalamic obesity in patients with pediatric craniopharyngioma.

Purpose: To identify the independent risk factors for developing morbid hypothalamic obesity, to propose a predictive scoring system for morbid hypothalamic obesity, and to propose an algorithm for management in order to minimize the risk of developing morbid hypothalamic obesity in patients with pediatric craniopharyngioma.

Methods: A retrospective analysis of all pediatric craniopharyngioma patients diagnosed and treated at Boston Children's Hospital (BCH) between 1985 and 2017. Analysis of the data was conducted using IBM SPSS Statistics.