Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma.
Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma.
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整合测序发现了一个ATF1基序富集的分子特征，可区分透明细胞癌和粘液样癌。
DOI：
10.1016/j.oraloncology.2021.105270
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发表时间：
2021-06
期刊：
影响因子：
4.8
通讯作者：
Brenner JC
中科院分区：
文献类型：
--
作者：
Heft Neal ME;Gensterblum-Miller E;Bhangale AD;Kulkarni A;Zhai J;Smith J;Brummel C;Foltin SK;Thomas D;Jiang H;McHugh JB;Brenner JC
唾液腺肿瘤由多种恶性肿瘤组成，预后差异很大。这些癌症可能难以区分，特别是在基于免疫组织化学（IHC）表征潜力有限的病例中。在这里，我们试图定义一种罕见的唾液腺癌，称为透明化透明细胞癌（HCCC）的分子特征，并确定能够区分HCCC和组织病理学上类似的疾病粘液表皮样癌（MEC）的分子基因特征。我们首次对5个独立的HCCC病例进行了完整的特征分析。我们在HCCC肿瘤中发现了胰岛素样生长因子的改变和IGF2和/或IGF1R的异常表达，提示可能依赖于这一途径。此外，我们还发现了一个354基因标记，该标记将HCCC与MEC区分开来，并且在其启动子中具有ATF1结合基序的基因显著富集，这支持了在这些肿瘤中发现的特征性EWSR1-ATF1融合的转录致病机制。在差异表达基因中，IGF1R、SGK1和SGK3在hcc中相对于mec升高。最后，免疫检查点和随后的免疫组化分析表明，CXCR4蛋白在一些HCCC病例中升高。总的来说，我们的数据确定了一个富含atf1基元的基因标记，这可能对HCCC与其他唾液腺肿瘤的分子分化具有临床应用价值，并发现潜在的可操作改变，这可能有利于复发性HCCC患者的临床护理。
Salivary gland tumors are comprised of a diverse group of malignancies with widely varying prognoses. These cancers can be difficult to differentiate, especially in cases with limited potential for immunohistochemistry (IHC)-based characterization. Here, we sought to define the molecular profile of a rare salivary gland cancer called hyalinizing clear cell carcinoma (HCCC), and identify a molecular gene signature capable of distinguishing between HCCC and the histopathologically similar disease, mucoepidermoid carcinoma (MEC). We performed the first integrated full characterization of five independent HCCC cases. We discovered insulin-like growth factor alterations and aberrant IGF2 and/or IGF1R expression in HCCC tumors, suggesting a potential dependence on this pathway. Further, we identified a 354 gene signature that differentiated HCCC from MEC, and was significantly enriched for genes with an ATF1 binding motif in their promoters, supporting a transcriptional pathogenic mechanism of the characteristic EWSR1-ATF1 fusion found in these tumors. Of the differentially expressed genes, IGF1R, SGK1 and SGK3 were found to be elevated in the HCCCs relative to MECs. Finally, analysis of immune checkpoints and subsequent IHC demonstrated that CXCR4 protein was elevated in several of the HCCC cases. Collectively, our data identify an ATF1-motif enriched gene signature that may have clinical utility for molecular differentiation of HCCCs from other salivary gland tumors and discover potential actionable alterations that may benefit the clinical care of recurrent HCCC patients.
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影响因子：
--
作者：
Qu X;Wu Z;Dong W;Zhang T;Wang L;Pang Z;Ma W;Du J
通讯作者：
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影响因子：
3.7
作者：
Antonescu, Cristina R.;Katabi, Nora;Weinreb, Ilan
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Weinreb, Ilan
影响因子：
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作者：
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通讯作者：
Shaw, Alice T.
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作者：
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通讯作者：
Brenner, J. Chad
影响因子：
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作者：
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通讯作者：
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