Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles
Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles
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DOI：
10.1038/s41379-018-0005-y
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发表时间：
2018-08-01
期刊：
影响因子：
7.5
通讯作者：
Homoe, Preben
中科院分区：
文献类型：
--
作者：
Andreasen, Simon;Tan, Qihua;Homoe, Preben
腺样囊性癌是涎腺和泪腺中最常见的恶性肿瘤之一，其预后以频繁的局部复发、远处转移和肿瘤相关死亡为特征。相反，乳腺腺样囊性癌是一种罕见的三阴性（雌激素和孕激素受体，HER 2）和基底样癌，与其他三阴性和基底样乳腺癌相比，预后非常好。无论部位如何，腺样囊性癌的特征在于涉及MYB、MYBL 1和NFIB的基因融合，不同临床结果的原因尚不清楚。为了确定临床结果差异的分子机制，我们对64例唾液腺、9例泪腺和11例乳腺腺样囊性癌的表型、基因重排模式和总体microRNA表达谱进行了表征。所有的乳腺和泪腺腺样囊性癌都有三阴性和基底样表型，而13%的唾液腺肿瘤不确定。在所有三个位置的大多数病例中发现MYB和/或NFIB的畸变，而MYBL 1的参与仅限于唾液腺中的肿瘤。总体microRNA表达谱将唾液腺和泪腺腺样囊性癌与其各自的正常腺体分开，但不能区分正常乳腺腺样囊性癌与正常乳腺组织。分层聚类将涎腺腺样囊性癌与乳腺腺样囊性癌分开，并将泪腺癌置于两者之间。对涎腺和乳腺腺样囊性癌之间差异表达的microRNA的功能注释显示，这些microRNA是参与代谢、信号转导的调控基因，也是参与其他癌症的基因。总之，microRNA失调是根据起源部位区分腺样囊性癌的第一类分子。这为探索腺样囊性癌的生物学提供了一个新的途径。
Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.