Cancer Predisposition Sequencing Reporter (CPSR)

Cancer Predisposition Sequencing Reporter (CPSR) interprets and classifies germline DNA variants identified by next-generation sequencing to report cancer predisposition and inherited cancer syndromes.

Key Features:

• Variant Classification: Applies a comprehensive classification system based on over 30 refined criteria from the American College of Medical Genetics and Genomics (ACMG) guidelines to distinguish pathogenicity with reported high sensitivity and specificity.
• Structured Reporting: Generates structured reports summarizing germline variants within known cancer predisposition genes.
• Customizable Gene Panels: Supports selection from more than 40 virtual gene panels curated by scientific experts to tailor the set of cancer predisposition genes analyzed.
• Incidental Findings Reporting: Reports incidental findings according to ACMG v3.0 recommendations.
• Actionable Secondary Variants: Identifies actionable secondary variant findings to inform potential therapeutic interventions.

Scientific Applications:

• Risk Management and Surveillance: Informs clinical risk management and surveillance strategies for individuals with identified predisposition variants.
• Surgical Decision Support: Provides variant information that can inform surgical decision-making in oncology.
• Treatment Guidance: Guides treatment plans, particularly when pathogenic variants are located in DNA repair genes.
• Biomarker Identification: Highlights markers of therapeutic, prognostic, and diagnostic relevance for personalized medicine approaches in oncology.

Methodology:

CPSR applies ACMG-based variant classification using over 30 refined criteria, enables analysis against more than 40 curated virtual gene panels, reports incidental findings per ACMG v3.0, identifies actionable secondary variants, and is implemented using Python and R with Docker for containerized execution.