Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma.
Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma.
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DOI：
10.1158/2159-8290.cd-15-0859
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发表时间：
2016-02
期刊：
影响因子：
28.2
通讯作者：
Ness SA
中科院分区：
文献类型：
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作者：
Brayer KJ;Frerich CA;Kang H;Ness SA
腺样囊性癌（ACC）是第二常见的唾液腺恶性肿瘤，是一种罕见的肿瘤，预后黯淡，治疗靶点不详。我们使用RNA测序（RNA-seq）分析来自档案，甲醛固定，石蜡包埋样品的低质量RNA。除了检测到最常见的ACC易位t（6;9）将MYB原癌基因与NFIB融合外，我们还分别检测到以前未知的t（8;9）和t（8;14）将MYBL1基因与NFIB和RAD51B基因融合的易位。RNA-seq提供了基因融合、备选RNA剪接和基因表达特征的信息。有趣的是，MYB和MYBL1易位的肿瘤表现出相似的基因表达谱，MYB和MYBL1的联合表达与预后相关，这表明相关的MYB蛋白在ACC中是可互换的致癌驱动因子。我们的研究结果提供了关于ACC生物学的重要细节，并说明了档案组织样本如何用于罕见肿瘤的详细分子分析。
Adenoid Cystic Carcinoma (ACC), the second most common malignancy of salivary glands, is a rare tumor with bleak prognosis for which therapeutic targets are unavailable. We used RNA-sequencing (RNA-seq) to analyze low-quality RNA from archival, formaldehyde-fixed, paraffin-embedded samples. In addition to detecting the most common ACC translocation, t(6;9) fusing the MYB proto-oncogene to NFIB, we also detected previously unknown t(8;9) and t(8;14) translocations fusing the MYBL1 gene to the NFIB and RAD51B genes, respectively. RNA-seq provided information about gene fusions, alternative RNA splicing and gene expression signatures. Interestingly, tumors with MYB and MYBL1 translocations displayed similar gene expression profiles, and the combined MYB and MYBL1 expression correlated with outcome, suggesting that the related Myb proteins are interchangeable oncogenic drivers in ACC. Our results provide important details about the biology of ACC and illustrate how archival tissue samples can be used for detailed molecular analyses of rare tumors.