临床下一代测序板揭示了默克尔细胞多瘤病毒阴性默克尔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
影响因子:1.90000
分区:医学4区 / 病理学3区
发表日期:2023 Apr 04
作者:
Emily Hartsough, Mari Mino-Kenudson, Jochen K Lennerz, Dora Dias-Santagata, Mai P Hoang
摘要
我们旨在确定默克尔细胞多瘤病毒（MCPYV）阴性默克尔细胞癌（MCCS）和神经内分泌癌（NECS）（NECS）的分子差异。分子测试。APC，MAP3K1，NF1，PIK3CA，RB1，ROS1和TSC1突变，除了高肿瘤突变负担和UV签名外，在MCPYV阴性MCC中经常注意到与小细胞NEC相比，与分析的所有NEC相比，MCPYV阴性MCC中经常分析，而KRAS突变则经常在大细胞中分析。尽管不敏感，但NF1或PIK3CA的存在特定于MCPYV阴性MCC。在大细胞NEC中，KEAP1，STK11和KRAS改变的频率明显更高。 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.尽管很少见，但基因融合的存在支持NEC。
Abstract
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.