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Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality.

The evolution of clinical trials for infant acute lymphoblastic leukemia

Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has...

Glioma-specific Domain IV EGFR cysteine mutations promote ligand-induced covalent receptor dimerization and display enhanced sensitivity

Epidermal growth factor receptor (EGFR) is over-expressed in many brain tumors. This paper examines mutations the EGFR that make the cell it is produced in...

Efficacy of acute myeloid leukemia therapy without stem-cell transplantation in a child with blastic plasmacytoid dendritic cell neoplasm

Our case demonstrates that AML therapy, without HSCT, can be sufficient to treat this rare disease in children.

Maternal Use of Folic Acid and Other Supplements and Risk of Childhood Brain Tumors

Interest in a possible protective effect of maternal vitamin use before or during pregnancy against childhood brain tumors (CBT) and other childhood cancers...

Chemotherapy increases amenability of surgical resection in congenital glioblastoma

Brain tumors presenting in infancy, especially during the first 6 months of life.

Identification of suitable endogenous control genes for microRNA expression profiling of childhood medulloblastoma and human neural stem cells

Medulloblastoma (MB) is the most common type of malignant childhood brain tumour.

Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma

Medulloblastoma (MB) consists of four core molecular subgroups with distinct clinical features and prognoses. Treatment consists of surgery, followed by radiotherapy and cytotoxic chemotherapy. Despite this intensive approach, outcome remains dismal for patients with certain subtypes of MB, namely, MYC-amplified Group 3 and TP53-mutated SHH. Using high-throughput assays, six human MB cell lines were screened against a library of 3208 unique compounds. We identified 45 effective compounds from the screen and found that cell cycle checkpoint kinase (CHK1/2) inhibition synergistically enhanced the cytotoxic activity of clinically used chemotherapeutics cyclophosphamide, cisplatin, and gemcitabine.

Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer

The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations.

RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational Status

PTEN mutation occurs in a variety of aggressive cancers and is associated with poor patient outcomes. Recent studies have linked mutational loss of PTEN to reduced RAD51 expression and function, a key factor involved in the homologous recombination (HR) pathway. However, these studies remain controversial, as they fail to establish a definitive causal link to RAD51 expression that is PTEN-dependent, while other studies have not been able to recapitulate the relationship between the PTEN expression and the RAD51/HR function.