Wang Shuhang, Chen Rongrong, Tang Yu, Yu Yue, Fang Yuan, Huang Huiyao, Wu Dawei, Fang Hong, Bai Ying, Sun Chao, Yu Anqi, Fan Qi, Gu Dejian, Yi Xin, Li Ning
Clinical Cancer Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Center, Geneplus-Beijing Institute, Beijing, China.
Front Oncol. 2020 Apr 21;10:536. doi: 10.3389/fonc.2020.00536. eCollection 2020.
Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcomes for patients with rare tumors. This study aims to discover opportunities for use of targeted therapies already approved for routine use in patients with rare tumors. Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiological data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal were compared with that of the Chinese population for targetable genomic alterations (TGAs). TGAs were defined as mutations of , and with level 1 to 4 of evidence according to the OncoKB knowledge database. Genomic data of 4,901 patients covering 63 subtypes of rare tumor from cBioPortal were used as the western cohort. The Chinese cohort was comprised of next generation sequencing (NGS) data of 1,312 patients from across China covering 67 subtypes. Forty-one subtypes were common between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioPortal cohort, and 53.43% (701/1312) in Chinese cohort ( < 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioPortal cohort (54.1%% vs. 26.1%, < 0.001). Generally, targetable mutations in were ≥3 times more frequent in Chinese cohort compared with that of the cBioPortal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with the highest number of TGAs per tumor. The incidence of TGAs in rare tumors was substantial worldwide and was even higher in our Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.
综合基因组分析对于制定新的治疗策略以及改善罕见肿瘤患者的治疗结果可能具有指导意义。本研究旨在发现将已获批用于罕见肿瘤患者常规治疗的靶向疗法加以应用的机会。在中国，基于流行病学数据和当前标准化治疗的可得性进行综合分析后，将年发病率低于2.5/10万的实体瘤定义为罕见肿瘤。将来自公共数据库cBioPortal的罕见肿瘤基因组数据与中国人群的基因组数据进行比较，以寻找可靶向的基因组改变（TGA）。根据OncoKB知识数据库，TGA被定义为具有1至4级证据的 、 和 的突变。来自cBioPortal的涵盖63种罕见肿瘤亚型的4901例患者的基因组数据用作西方队列。中国队列由来自中国各地的1312例患者的下一代测序（NGS）数据组成，涵盖67种亚型。两个队列共有41种亚型。cBioPortal队列中TGA的累积患病率为20.40%（1000/4901），中国队列中为53.43%（701/1312）（<0.001）。在这41种重叠亚型中，中国队列中的患病率仍显著高于cBioPortal队列（54.1%对26.1%，<0.001）。总体而言，中国队列中 可靶向突变的频率比cBioPortal队列高≥3倍。原发肿瘤类型不明的癌症、胃肠道间质瘤、胆囊癌、肝内胆管癌和肺肉瘤样癌是每种肿瘤中TGA数量最多的前5种肿瘤类型。罕见肿瘤中TGA的发生率在全球范围内都很高，在我国罕见肿瘤人群中甚至更高。综合基因组分析可能为解决罕见肿瘤患者选择有限的问题提供新的治疗模式。
