临床下一代测序面板揭示了梅尔克细胞聚病毒阴性梅尔克细胞癌和神经内分泌癌之间的分子差异。
Clinical Next-Generation Sequencing Panels Reveal Molecular Differences Between Merkel Cell Polyomavirus-Negative Merkel Cell Carcinomas and Neuroendocrine Carcinomas.
发表日期:2023 Feb 22
作者:
Emily Hartsough, Mari Mino-Kenudson, Jochen K Lennerz, Dora Dias-Santagata, Mai P Hoang
来源:
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
摘要:
我们旨在确定 Merkel 细胞多瘤病毒 (MCPyV) 阴性的 Merkel 细胞癌 (MCCs)和神经内分泌癌(NECs)之间的分子差异。我们的研究包括了56例MCC(28例 MCPyV 阴性,28例 MCPyV 阳性)和106例NEC(66例小细胞 NEC,21例大细胞 NEC,19例差分化程度差的 NEC)提交进行临床分子检测。APC、MAP3K1、NF1、PIK3CA、RB1、ROS1 和 TSC1 突变,以及高肿瘤突变负荷和 UV 特征,在 MCPyV 阴性 MCC 中与小细胞 NEC 和所有分析的 NEC 相比经常出现,而 KRAS 突变在大细胞 NEC 和所有分析的 NEC 中更经常出现。尽管不太敏感,但 NF1 或 PIK3CA 的存在特异性适用于 MCPyV 阴性 MCC。在大细胞 NEC 中 KEAP1、STK11 和 KRAS 变异率显著较高。在96个 NEC 中检测到 6.25%(6/96)的融合,但在45个分析的 MCC 中检测不到。高肿瘤突变负荷和 UV 特征,以及 NF1 和 PIK3CA 突变的存在,支持 MCPyV 阴性 MCC,而 KEAP1、STK11 和 KRAS 突变支持 NEC。虽然罕见,但基因融合的存在支持 NEC。©The Author(s) 2023。由牛津大学出版社代表美国临床病理学会出版。版权所有,未经许可不得使用。有关权限,请发送电子邮件至:journals.permissions@oup.com。
We aim to determine molecular differences between Merkel cell polyomavirus (MCPyV)-negative Merkel cell carcinomas (MCCs) and neuroendocrine carcinomas (NECs).Our study included 56 MCCs (28 MCPyV negative, 28 MCPyV positive) and 106 NECs (66 small cell NECs, 21 large cell NECs, and 19 poorly differentiated NECs) submitted for clinical molecular testing.APC, MAP3K1, NF1, PIK3CA, RB1, ROS1, and TSC1 mutations, in addition to high tumor mutational burden and UV signature, were frequently noted in MCPyV-negative MCC in comparison to small cell NEC and all NECs analyzed, while KRAS mutations were more frequently noted in large cell NEC and all NECs analyzed. Although not sensitive, the presence of either NF1 or PIK3CA is specific for MCPyV-negative MCC. The frequencies of KEAP1, STK11, and KRAS alterations were significantly higher in large cell NEC. Fusions were detected in 6.25% (6/96) of NECs yet in none of 45 analyzed MCCs.High tumor mutational burden and UV signature, as well as the presence of NF1 and PIK3CA mutations, are supportive of MCPyV-negative MCC, whereas KEAP1, STK11, and KRAS mutations are supportive of NEC in the appropriate clinical context. Although rare, the presence of a gene fusion is supportive of NEC.© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.