Authors
David A Fabrizio, Thomas J George Jr, Richard F Dunne, Garrett Frampton, James Sun, Kyle Gowen, Mark Kennedy, Joel Greenbowe, Alexa B Schrock, Aram F Hezel, Jeffrey S Ross, Phillip J Stephens, Siraj M Ali, Vincent A Miller, Marwan Fakih, Samuel J Klempner
Publication date
2018/8
Journal
Journal of gastrointestinal oncology
Volume
9
Issue
4
Pages
610
Publisher
AME Publications
Description
Background
The clinical application of PD1/PD-L1 targeting checkpoint inhibitors in colorectal cancer (CRC) has largely focused on a subset of microsatellite instable (MSI-high) patients. However, the proposed genotype that sensitizes these patients to immunotherapy is not captured by MSI status alone. Estimation of tumor mutational burden (TMB) from comprehensive genomic profiling is validated against whole exome sequencing and linked to checkpoint response in metastatic melanoma, urothelial bladder cancer and non-small cell lung carcinoma. We sought to explore the subset of microsatellite stable (MSS) CRC patients with high TMB, and identify the specific genomic signatures associated with this phenotype. Furthermore, we explore the ability to quantify TMB as a potential predictive biomarker of PD1/PD-L1 therapy in CRC.
Methods
Formalin-fixed, paraffin embedded tissue sections from 6,004 cases of …
Scholar articles
DA Fabrizio, TJ George Jr, RF Dunne, G Frampton… - Journal of gastrointestinal oncology, 2018