Bioinformatically Expanded Next-Generation Sequencing Analysis Optimizes Identification of Therapeutically Relevant MET Copy Number Alterations in >50,000 Tumors.

ABSTRACT:

Purpose

Clinical relevance thresholds and laboratory methods are poorly defined for MET amplification, a targetable biomarker across malignancies.

Experimental design

The utility of next-generation sequencing (NGS) in assessing MET copy number alterations was determined in >50,000 solid tumors. Using fluorescence in situ hybridization as reference, we validated and optimized NGS analysis.

Results

Incorporating read-depth and focality analyses achieved 91% concordance, 97% sensitivity, and 89% specificity. Tumor heterogeneity, neoplastic cell proportions, and genomic focality affected MET amplification assessment. NGS methodology showed superiority in capturing overall amplification status in heterogeneous tumors and defining amplification focality among other genomic

SUBMITTER: Solomon JP 

PROVIDER: S-EPMC9633455 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature