Abstract 742: Genomic alteration, tumor mutation burden and PD-L1 status of Chinese hepatic angiosarcoma patients
Authors: Luo Rongkui , Zhang Lili , Jiang Zhengzeng , Chen Lingli , Zhu Na , Hou Yingyong , Cui Qiang , Qu Yueting , Li Hong , Ji Yuan 
Published: August 2019

Abstract
Background:
Hepatic angiosarcoma is a rare and aggressive tumor which originating from endothelial cells in the liver. Known etiological factors include exposure to vinyl chloride, arsenic, androgenic-anabolic steroids and thorotrast, which was reported associated with mutation of TP53 and KRAS in angiosarcoma. Currently, there is a lack of data on the genomic profiling of hepatic angiosarcoma in Chinese population. We tried to mapping the mutation tendency of Chinese patients with hepatic angiosarcoma and provide the reference of targeted therapy or immunotherapy for these patients.
Methods:
Formalin Fixed Paraffin Embedded (FFPE) samples of 7 Chinese hepatic angiosarcoma patients were collected for next-generation sequencing (NGS)-based 458 genes sequence assay, and the medical history was recounted. Genomic alterations including single base substitution, copy number variations, gene fusions and rearrangement were assessed. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also analyzed by NGS algorithm. PD-L1 expression was detected by immunohistochemistry (IHC) assay (SP142).
Results:
None of these 7 patients, including 6 males and 1 female with median age of 61, had any contact with vinyl chloride, arsenic, androgenic-anabolic steroids or thorotrast. The most commonly altered genes were TP53 (6/7),ATRX (5/7),IGF1R amplification (2/7),LRP1B (2/7),NOTCH1 (2/7) and SETD2 (2/7). One patient was found contain substitution and amplification of KRAS. Several actionable genomic alterations were found in this study, including PIK3CA (1/7), CDKN2A/B (1/7), KDR (1/7), KIT (1/7) and PDGFRA (1/7). The frequency of ATRX alteration is relatively high, 5 out of 7 patients showed ATRX mutation. These mutations lead to ATRX inactivation which can induce telomerase instability. Meanwhile, the level of TMB was analyzed by 458 gene-related NGS targeted panel sequencing and it was found that 4 patients (57%) presented high TMB (&gt;10 muts/Mb), which is consistent with angiosarcoma in general. Interestingly, 3 TMB-H patients carried ATRX mutation at the same time. All of the samples were identified as microsatellite stability (MSS). IHC results showed that positive expressions of PD-L1 were found in 2 patients (TC 15%, IC 1%-3%).
Conclusions:
Our study firstly revealed the genomic profiling of Chinese hepatic angiosarcoma patients with no history of exposure with known etiological factors. Three patients harbored at least one actionable genomic alteration. Moreover, 3 of the 5 patients with ATRX mutation presented high TMB value, which shows that inactivation of ATRX may relevant to TMB-H. Overall, our results provide evidences for therapy strategy of hepatic angiosarcoma in China, especially patients with high TMB may potentially benefitted from immunotherapy.
Citation Format: Rongkui Luo, Lili Zhang, Zhengzeng Jiang, Lingli Chen, Na Zhu, Yingyong Hou, Qiang Cui, Yueting Qu, Hong Li, Yuan Ji. Genomic alteration, tumor mutation burden and PD-L1 status of Chinese hepatic angiosarcoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 742.