5' ALK Amplification in Neuroblastoma: A Case Report
Related Experiment Video
Updated: Nov 6, 2025
Zebrafish Model of Neuroblastoma Metastasis
Published on: March 14, 2021
Sara Akhavanfard1, Erik Nohr2, Mohammad AlNajjar3
1Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Insights
This case study highlights a neuroblastoma patient with complex genomic alterations. Careful interpretation of fluorescence in situ hybridization and array analysis is crucial for identifying high-risk neuroblastoma and guiding treatment.
Area of Science:
- Pediatric Oncology
- Cancer Genomics
- Molecular Diagnostics
Background:
- Neuroblastoma is a common infant cancer with variable outcomes.
- Genomic alterations like MYCN and ALK amplification indicate high-risk disease.
- Accurate genomic profiling is essential for risk stratification and treatment planning.
Observation:
- A 5-year-old male presented with metastatic neuroblastoma.
- Initial fluorescence in situ hybridization (FISH) suggested ALK gene alterations.
- Orthogonal methods revealed ALK exon gain and other unfavorable genomic features, including 17q gain and chromosome 12q amplification (CDK4, MDM2).
Findings:
- FISH findings for ALK gene alterations require careful interpretation and orthogonal validation.
- The patient exhibited multiple poor prognostic genomic markers.
- Combined genomic analysis identified complex genetic landscape in this neuroblastoma case.
Implications:
- Accurate detection of genomic alterations is critical for high-risk neuroblastoma classification.
- Advanced genomic techniques are vital for clarifying complex genetic findings.
- Precise genomic profiling aids in identifying potential therapeutic targets for neuroblastoma.
Abstract:
Neuroblastoma is the most common cancer in infants younger than 12 months of age, occurring with an incidence of 1 in 100,000 children. The clinical outcome of neuroblastoma ranges from spontaneous regression to treatment-resistant progression and/or metastasis, and accounts for 8-10% of childhood cancer deaths. Segmental chromosomal aberrations, as well as MYCN and ALK amplification, are among factors contributing to an unfavorable genomic profile and high-risk disease classification. Here, we describe a 5-year-old male who presented with a large right renal neuroblastoma tumor having lung and liver metastases. Fluorescence in situ hybridization analysis indicated the presence of >20 copies of the 5' region of the ALK gene in 26% of cells examined. Subsequent copy number assessment did not confirm ALK amplification, but revealed a gain of exons 2-5 of ALK, consistent with increased copy number for the 5' region of the ALK gene. Subsequent array analysis showed the presence of other unfavorable prognostic genomic features, including segmental gain of the 17q region and amplification of the long arm of chromosome 12 harboring CDK4 and MDM2, both reported to be poor prognostic indicators in patients with atypical clinical features in neuroblastoma. Taken together, this report illustrates the importance of careful interpretation of aberrant FISH findings and subsequent use of orthogonal methods to clarify the presence of genomic alterations to successfully determine potential treatment targets.
