DNA Damage Response and Repair (DDR) Gene Mutations and Correlation with Tumor Mutation Burden (TMB) in Non-Small Cell Lung Cancer (NSCLC)
Hirva Mamdani , Jerry Chen , Seongho Kim , Yahya Ibrahim , Rebecca Feldman , Jorge J Nieva, Abdul Rafeh Naqash , Stephen V Liu , Patrick C Ma, David C Portnoy , Hossein Borghaei , Nagla Abdel Karim , Yanis Boumber , Ari M Vanderwalde , Alexander I Spira , Shadia I Jalal
Loss of DNA repair fidelity is a common feature of human cancers and can drive genomic instability and tumor evolution.
DNA repair deficiency has emerged as a predictive biomarker of response to platinum based chemotherapy and PARP
More recently, DNA repair defects have been shown to predict response to immune checkpoint inhibitors.
Data on the relationship between DNA repair defects and TMB in NSCLC is limited.
Characterize the landscape of DNA damage response and repair (DDR) genes mutations in NSCLC
Correlate DDR gene mutations with immune biomarkers (TMB and PD-L1)
Identify mutations with the strongest association with high TMB
We retrospectively analyzed biomarker profiles of 5,667 NSCLC tumors that had undergone molecular profiling between 01/16 – 06/18 (Caris Life Sciences, Phoenix, AZ).
Profiling included next-generation sequencing of 592 genes, TMB, and PD-L1 expression by immunohistochemistry (22c3).