CHEK2 Alterations in Pediatric Malignancy: A Single-Institution Experience

Area of Science:

• Genetics
• Oncology
• Pediatrics

Background:

• Germline alterations in cancer-predisposing genes account for approximately 10% of pediatric malignancies.
• Checkpoint kinase 2 (CHEK2) germline loss-of-function variants are implicated in pediatric cancers, but their clinical impact remains unclear.

Purpose of the Study:

• To describe the clinical phenotypes and outcomes of pediatric oncology patients with CHEK2 germline alterations.
• To review existing data on CHEK2 variants in pediatric cancer and discuss challenges in interpretation and genetic counseling.

Main Methods:

• Retrospective chart review of pediatric oncology patients with identified CHEK2 germline alterations.
• Analysis of clinical presentations, disease course, and outcomes at a single institution.

Main Results:

• Six pediatric patients with CHEK2 germline variants were identified from a cohort of 300 individuals.
• Tumor types included Burkitt lymphoma, neuroblastoma, brain tumors, Ewing sarcoma, and myelodysplastic syndrome.
• Outcomes varied, with some patients achieving remission, one undergoing treatment, and one developing treatment-related meningiomas.

Conclusions:

• CHEK2 germline loss-of-function alterations are associated with a spectrum of pediatric tumors.
• Larger, multicenter studies are necessary to fully elucidate the incidence, phenotype, and molecular biology of CHEK2 variants in pediatric cancers.