Abstract 4811
Background
Thymic carcinomas (TC) is a kind of a malignant intrathoracic tumor. Herein, we examined the clinicopathological characteristics and analyzed comprehensive genomic profiling (CGP) in 47 TC patients to elucidate the potentially clinically relevant genomic alterations (CRGAs) in this population.
Methods
47 stage I-IV TC patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017 were analyzed. These patients were sequenced by FoundationOne CDx (F1CDx) which is a FDA approved platform conducted by DIAN (Hangzhou Lab) with the licensed technologies. In this study, we focus on CRGAs which are known or likely pathogenic alterations.
Results
The 47 TC patients included 27 thymic squamous cell carcinoma (TSCC), 14 neuroendocrine tumors of the thymus (NETT) and 7 mixed subtype of TSCC and NETT. The median age of TSCC, NETT and mixed subtype was 59.5, 65 and 74, respectively. The median number of CRGAs in TSCC, NETT and mixed subtype were 1 (range 0-10), 2 (range 0-3) and 2 (range 0-4), respectively. Only one TSCC patient was microsatellite instability-high (MSI-H), which also has the highest TMB (21 Muts/Mb). Among all the four patients with TMB larger than 10 Muts/Mbs, three were TSCC and one was mixed subtype. 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%). Furthermore, 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.
Conclusions
This was the largest cohort of CGP for TC till now in a sample Chinese population. TSCC and NETT have very different mutated landscapes, while the mixed subtype was more similar with TSCC. The number of CRGA range from 0 to 10 also demonstrated a high tumor heterogeneity for TSCC. In addition, the top mutated genes in TSCC and NETT founded in this study were different from the published results which focused on metastatic thymic carcinoma (mTC). Given the limited treatment options and poor prognosis of patients with TC, CGP has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Shanghai science and technology commission.
Disclosure
All authors have declared no conflicts of interest.
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