Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in...

Area of Science:

• Genomics
• Oncology
• Bioinformatics

Background:

• Personalized oncology relies on identifying actionable genomic variants, but current next-generation sequencing (NGS) approaches are often complex and not widely scalable.
• Existing targeted NGS methods may not cover all critical genomic alteration classes relevant to solid tumors.

Purpose of the Study:

• To develop a scalable and comprehensive NGS-based assay for detecting predefined somatic genomic variants in solid tumors.
• To create an integrated system that links identified variants to potential targeted treatments, clinical guidelines, and trials.

Main Methods:

• A comprehensive bioinformatics analysis of over 700,000 samples defined a catalog of relevant somatic variants (mutations, copy number alterations, gene fusions).
• The Oncomine Comprehensive Panel (OCP), an NGS assay requiring minimal DNA/RNA from FFPE tissues, was developed to detect these variants.
• An informatics pipeline and knowledge base were created to identify variants and associate them with treatment strategies and clinical trial information.

Main Results:

• OCP validation demonstrated >95% accuracy for detecting key mutations (KRAS, EGFR, BRAF) and fusions (ALK, TMPRSS2:ERG) in over 300 FFPE samples.
• Between 6% and 42% of profiled solid tumors harbored actionable alterations beyond routine testing, linked to approved or guideline-referenced therapies.
• The OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers, showcasing its utility as a translational research tool.

Conclusions:

• The Oncomine Comprehensive Panel (OCP) offers a simplified and broadly applicable targeted NGS solution for precision oncology.
• By predefining somatic variants and compiling treatment strategies, OCP facilitates the advancement of personalized cancer care.