P70.14 PRKDC Mutations Recurrently Found in Non-Small Cell Lung Cancer in East Asian Patients

Abstract

Protein kinase, DNA-activated, catalytic polypeptide (PRKDC) encodes a 465 kDa catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) that plays a pivotal role in the maintenance of genomic stability and is a critical component of DNA double-strand break repair and recombination. Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. The aim of this study is to investigate mutations and prognosis of NSCLC harboring PRKDC mutations. A total of 328 patients with non-small-cell lung cancer were recruited between July 2012 and December 2018. The status of PRKDC mutations and other genes were detected by next generation sequencing. PRKDC gene mutation rate was 1.22% (4/328) in non-small cell lung cancer, including D3411N(1 patient), D2724H(1 patient), M4002L(1 patient) and A1634T(1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were PRKDC gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=2) co-occurring BCOR mutations had a median OS of 15.5 months and 22.0 months respectively (P=0.64); patients with (n=2) or without (n=2) co-occurring TP53 mutations had a median OS of 12.5 months and 19.0 months respectively (P=0.23); patients with (n=2) or without (n=2) co-occurring ARID1A mutations had a median OS of 17.5 months and 14.0 months respectively (P=0.81); patients with (n=2) or without (n=2) co-occurring KRAS mutations had a median OS of 12.5 months and 19.0 months respectively (P=0.23). BCOR, TP53, ARID1A, KRAS gene accompanied may have less correlation with PRKDC mutation in NSCLC patients. Next generation sequencing provides a simplified strategy and reasonably high detection rate for PRKDC mutation, which suggested application of the strategies into clinical molecular diagnostics.