Enhancing MET Copy Number Estimation by Factoring in Tumor Purity and Variant Types

The Mesenchymal Epithelial Transition factor gene (MET) is a crucial proto-oncogene implicated in cancer initiation and metastasis. Copy number amplification is a primary form of MET aberration, commonly occurring as focal amplification and polysomy. Despite NGS techniques being capable of identifying MET gene amplification, accurately quantifying its absolute copy number remains challenging. Specifically, NGS-based detection often exhibits lower concordance with the gold-standard Fluorescence in Situ Hybridization and lacks the ability to distinguish between amplification types. This paper presents a novel NGS-based approach designed to accurately quantify the copy number of MET gene amplification by incorporating tumor purity and variant classification considerations, thereby enhancing reliability. Our approach includes evaluating tumor cell content, converting observed MET gene copy numbers to absolute gene copy numbers (GCN), and differentiating between focal amplification and polysomy forms of MET amplification. The proposed approach has been evaluated on the real sequencing dataset. The results indicate that our approach significantly improves the precision of MET amplification status estimation via NGS, making it more consistent with FISH benchmark results.