Diagnostic application of high resolution single nucleotide polymorphism array analysis for children with brain...

Area of Science:

• Oncology
• Genetics
• Pediatrics

Background:

• Single nucleotide polymorphism (SNP) array analysis is a primary diagnostic method for pediatric brain tumors at The Children's Hospital of Philadelphia.
• This report details findings from 100 consecutive pediatric brain tumor cases.

Purpose of the Study:

• To summarize the utility of SNP array analysis in diagnosing pediatric brain tumors.
• To identify common and novel genetic alterations in various pediatric brain tumor types.
• To assess the role of SNP array analysis in refining diagnoses, prognoses, and guiding germline testing referrals.

Main Methods:

• SNP array analysis was performed on 100 pediatric brain tumor samples.
• Pathologic examination and targeted molecular analyses (Sanger sequencing) were integrated.
• Copy number alterations, gene fusions, and loss of heterozygosity were analyzed.

Main Results:

• Eighty-seven percent of tumors exhibited at least one pathogenic copy number alteration.
• KIAA1549-BRAF fusion (duplication in 7q34) found in 19/56 low-grade gliomas (LGGs).
• FAM131B-BRAF fusion (7q34 deletion) in pilocytic astrocytoma (PA) and dysembryoplastic neuroepithelial tumor (DNT).
• MYB-QKI fusion (6q23.3q26 deletion) in one ganglioglioma (GG).
• Specific chromosomal gains (5, 6, 7, 11, 20) in a subset of LGGs.
• Medulloblastomas (MBs) showed monosomy 6, 9q/10q deletions, and i(17)(q10).
• TP53, RB1, CDKN2A/B, CHEK2, NF1, NF2 alterations identified, prompting germline testing recommendations.
• BRAF mutations (p.Thr599dup, p.V600E) in gliomas; somatic TP53 mutation in a fibrillary astrocytoma; no TP53 mutations in MBs.

Conclusions:

• SNP array analysis is highly effective in detecting pathogenic alterations in pediatric brain tumors.
• Integrated analysis refines diagnoses, improves prognostic accuracy, and identifies patients needing germline testing.
• This approach enhances personalized medicine for pediatric brain tumor patients.