Background: Despite the high mortality associated with angiosarcoma, its low prevalence has limited sample sizes in prior studies. To address these gaps, we analyzed the AACR Project GENIE registry, a large, multi-institutional database. Methods: 359 tumor samples from 346 patients with angiosarcoma were identified from the AACR Project GENIE v18.0-public database using cBioPortal. Somatic mutations and copy number alterations were assessed. Statistical significance was assessed byt-test for continuous variables and a chi-squared test for categorical data, with significance set atp< 0.05. Results: Recurrent mutations includedTP53(20.6%),KDR(13.6%), andPIK3CA(10.6%). Copy number alterations occurred inMYC(27.3%),CRKL(10.4%),FLT4(5.5%), andKDR(4.8%). Homozygous deletions occurred inCDKN2A(6.6%),CDKN2B(6.56%), andMTAP(3.81%). Significant co-occurrence includedFAT1-NOTCH2,TP53-ATRX, andNOTCH1-ARID1A. Mutual exclusivity was seen withKDR-FLT4andKDR-ATRX. Females exhibited enrichment inMYCandHRAS, while males exhibited enrichment inPOT1,NTRK2, andFAT1. Compared with primary tumors, metastatic tumors more often displayedZFHX4,FGFR1,MSI2,HIST1H1C, andTOP1mutations, whileMAPK7mutations occurred only in primary tumors. Conclusions: In one of the largest genomic analyses of angiosarcoma to date, we identified recurrent alterations, suggesting potential future therapeutic targets.
背景：尽管血管肉瘤具有高死亡率，但其低发病率限制了既往研究的样本量。为弥补这一不足，我们分析了AACR项目GENIE注册库——一个大型多机构数据库。方法：通过cBioPortal平台从AACR项目GENIE v18.0公共数据库中筛选出346例血管肉瘤患者的359份肿瘤样本。评估体细胞突变和拷贝数变异情况。连续变量采用t检验，分类数据采用卡方检验进行统计学分析，显著性水平设定为p<0.05。结果：高频突变包括TP53（20.6%）、KDR（13.6%）和PIK3CA（10.6%）。拷贝数变异主要涉及MYC（27.3%）、CRKL（10.4%）、FLT4（5.5%）和KDR（4.8%）。纯合性缺失发生在CDKN2A（6.6%）、CDKN2B（6.56%）和MTAP（3.81%）。显著共现突变包括FAT1-NOTCH2、TP53-ATRX和NOTCH1-ARID1A。互斥突变见于KDR-FLT4和KDR-ATRX。女性患者中MYC和HRAS富集，而男性患者中POT1、NTRK2和FAT1富集。与原发肿瘤相比，转移性肿瘤更常出现ZFHX4、FGFR1、MSI2、HIST1H1C和TOP1突变，而MAPK7突变仅见于原发肿瘤。结论：通过迄今最大规模的血管肉瘤基因组分析，我们发现了高频变异模式，为未来潜在治疗靶点的开发提供了方向。
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