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Abstract Next-generation sequencing (NGS) for the detection of somatic variants has become the tool of choice in a variety of molecular oncology fields and in the clinic. Its use ranges from sequencing entire tumor genomes and transcriptomes to targeted clinical diagnostic gene panels. The NYU Langone Genome PACT assay is a qualitative in vitro diagnostic test that uses targeted next generation sequencing of formalin-fixed paraffin-embedded (FFPE) tumor tissue matched with normal specimens from patients to detect gene alterations in a 607-gene panel. Indications for testing are cancer (solid tumors or hematological malignancies) where a mutational profile from multiple genes would be informative for disease stratification, prognosis, or treatment options including targeted therapies and eligibility for clinical trials. The test is intended to provide information on somatic mutations including point mutations, copy number aberrations, and small insertions/deletions (indels) for diagnostic and treatment decisions. LG-PACT is a United States Food and Drug Administration (FDA) approved diagnostic test. The clinical interpretation of sequencing data of molecular tumor markers from NGS encompasses automated variant calling tools with human interpretation. The final mostly manual review of data is intensive, involving highly trained scientists, encompassing literature review, interpretation and tier classification by pathologists, who then provide a complete molecular diagnostic report to the treating oncologists. Since January 2022 to present (October 2023) we have provided clinical genomic reports for 1029 oncological cases from 124 different cancers and their subtypes, including Brain (489 cases incl. meningioma, glioma and glioblastoma), Gastrointestinal (123), Lung (114), among others. We first present the technical challenges of validating an NGS oncological diagnostic targeted assay for appropriate clinical grade accuracy and sensitivity acceptable for patient care. We show how copy number alterations provide a more comprehensive description of the tumors genomic profile. We then outline the actionability of targeted panel sequencing for our current patient cohort. Where analysis of variant detection has led to 47% (490) of our clinical tumor samples containing known tier 1 therapeutic variants. We conclude with presenting case studies that identify both the clinical utility and informatic challenges of variant calling specific to gene panel sequencing e. g. , i) the capture of potential targetable rare and novel indels and multivariant mutations in exons 19 and 20 of EGFR, and ii) a unique KIT tandem duplication event in a gastrointestinal stromal tumor (GIST). We demonstrate the value in precision oncology for multiple cancer types and how the capture of unique variants can provide better targeted treatment options to cancer patients. Citation Format: Varshini Vasudevaraja, Yiying Yang, Jonathan Serrano, Kazimierz Wrzeszczynski, Matija Snuderl. NYU Langone Genome PACT - Genome Profiling of Actionable Cancer Targets (LG-PACT) for clinical patient molecular diagnostics and treatment abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1771.
Vasudevaraja et al. (Fri,) studied this question.