Parental Pesticide Exposure and Childhood Brain Cancer: A Systematic Review and Meta-Analysis Confirming the IARC/WHO Monographs on Some Organophosphate Insecticides and Herbicides

Background: Brain tumors are the second most common neoplasm in the pediatric age. Pesticides may play an etiologic role, but literature results are conflicting. This review provides a systematic overview, meta-analysis, and IARC/WHO consideration of data on parental exposure to pesticides and childhood brain tumors. Methods: We searched PubMed, SCOPUS, and Google Scholar for literature (1 January 1966–31 December 2020) that assessed childhood brain tumors and parental exposure to pesticides. We undertook a meta-analysis addressing prenatal exposure, exposure after birth, occupational exposure, and residential exposure. A total of 130 case-control investigations involving 43,598 individuals (18,198 cases and 25,400 controls) were included. Results: Prenatal exposure is associated with childhood brain tumors (odds ratio, OR = 1.32; 95% CI: 1.17–1.49; I2 = 41.1%). The same occurs after birth exposure (OR = 1.22; 95% CI: 1.03–1.45, I2 = 72.3%) and residential exposure to pesticides (OR = 1.31; 95% CI: 1.11–1.54, I2 = 67.2%). Parental occupational exposure is only marginally associated with CBT (OR = 1.17, 95% CI: 0.99–1.38, I2 = 67.0%). Conclusions: There is an association between CBT and parental pesticides exposure before childbirth, after birth, and residential exposure. It is in line with the IARC Monograph evaluating the carcinogenicity of diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos.

OMIC-13. THE ROLE OF COPY NUMBER ALTERATIONS IN PREDICTING SURVIVAL AND INFLUENCING TREATMENT OF CHILDHOOD BRAIN TUMORS

Brain and central nervous system tumors are the most common form of solid tumor cancers and the second most common cancer overall among children. While many advances have been made in understanding the genomics of childhood brain tumors in recent years, the role of copy number alterations (CNAs) has not been fully characterized. Although the genomes of childhood brain tumor patients are generally considered to be relatively stable diploid genomes, analysis of a subset of pretreatment diagnostic samples from a cohort of 84 deceased patients from Washington University revealed widespread alterations, suggesting CNAs may play a larger role in the progression and prognosis of childhood brain tumors than originally thought. Follow up analysis of the entire cohort, containing a variety of tumor types that had low-pass whole genome sequencing performed, similarly showed evidence of CNAs across samples. 75 out 84 patients showed the presence of CNAs with an average of 16% of the genome being altered per sample and a median of 7%. Preliminary results examining correlations between the percentage of the genome that was copy number altered and event free survival or overall survival indicated that CNA percentage may have some prognostic value. For example, ependymoma samples showed positive correlation between alteration percentage and overall survival, while glioblastoma samples showed negative correlation. To explore copy number alteration in a larger cohort and increase statistical power, similar analyses are being performed using an additional 950 samples from the Pediatric Brain Tumor Atlas curated by The Children’s Brain Tumor Network (CBTN) to determine if CNVs and CNV percentage or specific alterations can serve as prognostic markers and whether the biology of this genomic instability could inform therapeutic strategy.

Loss of nuclear envelope phosphatase CTDNEP1 drives aggressive medulloblastoma by triggering MYC amplification and genomic instability

MYC-driven medulloblastomas are highly aggressive childhood brain tumors, however, the genetic events triggering MYC amplification and malignant transformation remain elusive. Here we report that mutations in CTDNEP1, a CTD nuclear-envelope-phosphatase, are the most significantly enriched recurrent alterations in MYC-driven medulloblastomas, and define high-risk subsets with poorer prognosis. CTDNEP1 ablation transforms murine cerebellar progenitors into MYC-amplified medulloblastomas, resembling their human counterparts. CTDNEP1 deficiency stabilizes MYC protein by elevating MYC serine-62 phosphorylation, and triggers genomic instability with eventual MYC amplification and p53 loss. Further, phosphoproteomics reveals that CTDNEP1 post-translationally modulates the activities of key regulators for proper chromosome segregation and mitotic checkpoints including topoisomerase TOP2A and checkpoint kinase CHEK1. Co-targeting CHEK1 and MYC activities synergistically inhibits CTDNEP1-deficient MYC-amplified tumor growth and prolongs animal survival. Together, our studies identify CTDNEP1 acting as a tumor suppressor in highly aggressive medulloblastomas by maintaining homeostatic MYC levels and genomic stability, highlighting a CTDNEP1-dependent therapeutic vulnerability.

Delayed Diagnosis of Childhood Brain Tumors in Kenyatta National Hospital

Background: Brain tumors are the second commonest tumors after leukemia and the most common solid tumors in children. Childhood brain tumors are the most common cause of cancer-related deaths in children. Delayed diagnosis is associated with increased morbidity and mortality. Currently, there are no specific studies on this subject in Kenya.

Pineal Atypical Teratoid Rhabdoid Tumor in a 5-Month-Old Child

<b><i>Introduction:</i></b> Atypical teratoid rhabdoid tumors (ATRT), an uncommon malignant intracranial tumor with aggressive behavior are mostly seen in posterior fossa in young pediatric age-group. <b><i>Case Presentation:</i></b> We present an infrequent location of this tumor in the pineal region in a 5-month-old infant. Also, the lesion was non-enhancing which was highly atypical of an ATRT. It was near-totally excised with the child placed in sitting position. However, within a short interval, a tumor recurrence was noted. <b><i>Conclusion:</i></b> The case possibly represents an extended spectrum of congenital childhood brain tumors. Importantly, it highlights an atypical imaging of ATRT in very young children.