88. Clinical impact of targeted genomic profiling

Aly Abdelkareem

Thuy Phung

Thuy Phung, MD, PhD is medical director of molecular pathology & dermatopathology at the University of South Alabama in Mobile, AL.  She is spearheading efforts to enhance molecular diagnostics for cancer patients in southern Alabama by establishing rapid single-gene testing as well as actionable, cost-efficient next generation sequencing (NGS) assays.  She is the lead author of Pediatric Dermatopathology, a comprehensive textbook in the field.  In addition to her clinical and scientific work, Dr. Phung is passionate about global health.  She is a co-founder of the award-winning Vascular Anomalies Center in Ho Chi Minh City, Vietnam, which cares for thousands of underserved children with vascular anomalies.  Dr. Phung also leads a program in global pathology to enhance the standards of pathology practice in Vietnam.


Thuy Phung, Christian Manganti, Mohan Kasukurthi, Kelly Hebert, Jingshan Huang

University of South Alabama, Mobile, AL, United States

Next-generation sequencing (NGS) assays for solid tumors range from those that assess dozens of genes with actionable clinical utility (targeted genomic profiling, TGP) to assays that evaluate hundreds of genes (comprehensive genomic profiling, CGP). Genes included in TGP are limited in number and carefully chosen based on their clinical actionability with prognostic and/or therapeutic impact. Our goal is to determine the degree of difference in clinical impact of TGP as compared with CGP.

We analyzed 775 unique CGP cases. CGP covered ~500 genes with variant types including single nucleotide variants, copy number variants, indels and gene fusions. Pathogenic variants extracted from CGP cases included variants with FDA-approved therapy or standard-of-care, and variants in clinical trials specific for cancer type. Pathogenic variants identified in CGP cases were matched with those covered by TGP of 60 key cancer-related genes.

Actionable variants were identified in 112 out of 775 (14%) CGP cases across multiple tumor types. Among these 112 CGP cases, 108 cases (96%) had variants that were covered in TGP. There were 348 of 775 (45%) CGP cases with pathogenic variants indicative for cancer-specific and mutation-specific clinical trials. Among these 348 CGP cases, 235 cases (68%) had variants that were covered in TGP across multiple tumor types. TGP covers 96% of actionable mutations, and provides significant coverage (68%) of clinical-trial eligible variants identified by CGP. These findings show significant impact of TGP with respect to clinical utility, cost effectiveness, manageable gene content, and limited tissue resources.