P26.05 Comprehensive Genomic Sequencing in Thymic Epithelial Tumors: Identification of Multiple Poor Prognosis Biomarkers in Chinese Patients

Abstract

Thymic squamous carcinomas (TSCC) and thymic neuroendocrine tumor (NETT) are two types of thymic tumor which have higher risk of relapse and death. TSCC is a malignant neoplasm of the thymus with morphological features of squamous cell carcinoma as seen in other organs. However, the research about genetic profile and its relationship with prognosis of both tumors are rare. 47 patients who diagnosed with TSCC/NETT at Shanghai Jiao tong University Affiliated Chest Hospital between 2015 and 2017 were sequenced by FoundationOne CDx (F1CDx) which is a FDA approved platform conducted by DIAN (Hangzhou Lab) with the licensed technologies. During the follow up, the clinical information and the survival information was also collected. The cox regression model was used to analyze the relationship between genomic alteration and the survival data. A total of 47 patients’ (including 29 men, 14 ever smokers) surgical specimens were sequenced. The histological types include TSCC(N=27), NETT (N=14) and mixed of both(N=6). The median age of TSCC, NETT and mixed subtype was 59.5, 65 and 74, respectively. The top ranked altered genes in TSCC were TP53 (30%), CDKN2A (26), CDKN2B (19%) and ASXL1 (15%). In NETT, the top mutated genes were MEN1 (36%), STAG2 (14%), CDKN2A (14%) and HRAS (14%). The top ranked mutated genes in mixed subtype were TP53 (29%) and CDKN2A (29%). Notably, TP53, ASXL1, TET2, MLL2, EP30, BAP1 were only mutated in TSCC or mixed subtypes. However, mutated of MEN1, STAG2 and HRAS were also founded in NETT subtype. The TMB of three groups have no significant differences. 13 of 47 patients (27.7%) showed CDKN2A deletion and 7 of 47 tumors (14.9%) showed CDKN2B deletion which both were correlated with worse recurrence-free survival (RFS) (P<0.001). 5 (10.6%) patients showed MTAP loss, which was correlated with worse RFS (P =0.018). 6 (12.8%) patients showed TSC2 missense, which was correlated with worse RFS (P =0.017). 3 (6.4%) patients showed EPHB4 missense, which was also correlated with worse RFS (P =0.0081). Our study found that: TSCC and NETT have very different gene alternation landscape, while the mixed subtype was more similar with TSCC than with NETT. The most altered genes are focused on signal pathways of cell cycle control, Chromatin remodeling/DNA methylation, PI3K/AKT1/MTOR, MAP kinase signaling and others.In addition, we firstly identified multiple poor prognosis biomarkers in Chinese thymic epithelial tumors patients. These poor prognosis biomarkers are mainly enriched in cell cycle control and PI3K/AKT1/MTOR pathways.