D depth and GLP-2 Receptor Proteins Biological Activity evenness of coverage for WES sequencing. SeqPlus was used to sequence primary and relapsed tumor FFPE samples from a Kininogen-1 Proteins Species number of diverse cancer sorts to execute MSI, TMB, and associated analyses. Working with precisely the same tissue, we also measured mRNA expression by RNA-Seq and DNA methylation by array analysis. Results Similar to preceding studies, we located that, for the majority of samples, low MSI status and low TMB correlate. We also identified that, whilst higher MSI and elevated TMB often correlate, samples with high TMB using a low or stable MSI status are much more typical. A majority of samples without the need of MMR mutations have alterations in one or far more genes in other DNA repair pathways. Additional analysis will examine correlations in between repair gene expression and mutation burden status to investigate discrepancies e.g., samples with elevated TMB and higher MSI without MMR mutations. The influence of MSI and the TMB statusJournal for ImmunoTherapy of Cancer 2018, six(Suppl 1):Web page 314 ofon DNA methylation will also be examined for essential genes in a global measure of genome disruption in samples Conclusions Our data demonstrate the feasibility of using WGS of FFPE samples to enable patient selection methods for immune checkpoint inhibitor therapies. Our method could be beneficial in typical clinical care or trials in the future and facilitate retrospective analysis of archival FFPE cancer tissues. This approach will improve our understanding of genomic features that respond to immuno-oncology, targeted, or traditional therapies. P582 Implications of ARID1A deficiency on tumor microenvironment and immune landscape in non-small cell lung cancer (NSCLC) Young Kwang Chae, MD1, Pedro Viveiros, MD1, Bhoomika Sukhadia, MD1, Lee Chun Park, MD1, Muhammad Mubbashir Sheikh, MBBS / MD1, Jeffrey Chuang2 1 Northwestern University Feinberg College of Medicine, Chicago, IL, USA; two The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA Correspondence: Young Kwang Chae ([email protected]) Journal for ImmunoTherapy of Cancer 2018, 6(Suppl 1):P582 Background AT-rich interactive domain-containing gene 1A (ARID1A) will be the most regularly mutated gene inside the SWI/SNF chromatin remodeling loved ones [1, 2], involved in transcription regulation and DNA repair. Loss of function of ARID1A is related with disruption of mismatch repair [2] and poor prognosis in many solid tumors, especially gastrointestinal [3,4] and gynecological cancers [5]. Because of its tumor suppressor nature, it was believed to become a poor therapeutic target [2]. Recently, ARID1A deficiency was shown to be connected with increased CD8 Tcell infiltration and expression of programmed death-ligand 1 (PDL1) in ovarian cancer [2], implying the potential of ARID1A as a predictor of response to immune checkpoint inhibitors (ICIs). Since the role of ARID1A has not been explored in NSCLC, we investigated how ARID1A deficiency affected tumor microenvironment and immune landscape in these patients. Approaches We obtained ARID1A mRNA levels for NSCLC samples [Adenocarcinoma (ADC), n=517; Squamous cell carcinoma (SqCC), n= 501] from TCGA. The data was arranged into four quartiles primarily based on ARID1A expression derived from mRNA-seq z-scores, defining the lowest quartile (Q1) as low ARID1A and highest quartile (Q4) as high ARID1A. We examined how ARID1A expression levels correlated with a) PD-L1 expression and b) microsatellite analysis for normal-tumor instability (MANTIS) score [6]. We also evaluated tumor mutational burden (TMB), n.
