[NGS-based multi-gene panel testing in hematological malignancies: germline variants and related issues]

Area of Science:

• Oncology
• Genetics
• Hematology

Background:

• Gene panel testing, established in solid tumors, is nearing adoption in hematologic malignancies.
• Comprehensive gene panels can detect incidental germline variants, termed "secondary findings."
• These secondary findings may include disease-predisposing germline variants.

Purpose of the Study:

• To outline key issues surrounding germline variants detected by gene panel testing in hematologic oncology.
• To discuss challenges including detection, informed consent, disclosure scope, and genetic counseling.
• To highlight specific concerns related to donor germline variants in allogeneic hematopoietic stem cell transplantation.

Main Methods:

• Discussion of germline variant issues presented at a symposium.
• Focus on next-generation sequencing (NGS)-based multi-gene panel testing.
• Consideration of challenges in the context of hematologic tumors and transplantation.

Main Results:

• Gene panel testing in hematologic tumors presents unique challenges regarding germline variants.
• Detection, consent, disclosure, and counseling require careful consideration.
• Donor germline variants in allogeneic stem cell transplantation add complexity.

Conclusions:

• The integration of gene panel testing into hematologic oncology necessitates addressing germline variant implications.
• Standardized approaches for managing secondary findings and donor variants are needed.
• Further discussion and guideline development are essential for responsible implementation.