血管肉瘤异质性和免疫检查点阻断治疗的潜在脆弱性：来自基因组测序的见解。
Angiosarcoma heterogeneity and potential therapeutic vulnerability to immune checkpoint blockade: insights from genomic sequencing.
机构信息
Center for Personalized Cancer Therapy, University of California, Moores Cancer Center, La Jolla, CA, 92093, USA.
Divison of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
出版信息
Genome Med. 2020 Jul 9;12(1):61. doi: 10.1186/s13073-020-00753-2.
BACKGROUND
Angiosarcoma is an aggressive tumor. Recent case series describe exceptional responses to checkpoint blockade in this disease.
METHODS
Herein, we explored the genomic correlates of 48 angiosarcomas from the Angiosarcoma Project (12,499 variants analyzed in 6603 genes; whole-exome sequencing) versus 10,106 pan-cancer tumors in The Cancer Genome Atlas including 235 sarcomas but no angiosarcoma.
RESULTS
At the molecular level, angiosarcomas were heterogeneous. Those located in the face and scalp presented high tumor mutation burden, missense amino acid variations biased towards more hydrophobic (and therefore more immunogenic) peptides, and ultra-violet mutational signature.
CONCLUSIONS
Angiosarcoma molecular features are similar to those observed in melanoma and other skin tumors and may explain comparable immunotherapy sensitivity of these tumor types.
背景
血管肉瘤是一种侵袭性肿瘤。最近的病例系列描述了在这种疾病中检查点阻断的异常反应。
方法
在此，我们探索了血管肉瘤项目（在 6603 个基因中分析了 12499 个变体；全外显子组测序）的 48 个血管肉瘤与包括 235 个肉瘤但没有血管肉瘤的癌症基因组图谱中的 10106 个泛癌肿瘤的基因组相关性。
结果
在分子水平上，血管肉瘤具有异质性。那些位于面部和头皮的肿瘤具有高肿瘤突变负担、偏向更多疏水性（因此更具免疫原性）肽的错义氨基酸变化，以及超紫外线突变特征。
结论
血管肉瘤的分子特征与黑色素瘤和其他皮肤肿瘤观察到的特征相似，这可能解释了这些肿瘤类型对免疫治疗的敏感性相当。
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