Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression
Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression
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DOI：
10.1038/labinvest.2014.59
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发表时间：
2014-06-01
影响因子：
5
通讯作者：
Hermsen, Mario
中科院分区：
文献类型：
--
作者：
Costa, Ana F.;Altemani, Albina;Hermsen, Mario
腺样囊性癌偶尔会发生去分化，这种现象也被称为高级别转化。然而，腺样囊性癌的病例已被描述为向腺癌的转化，而不是低分化的，这表明高级别转化不一定反映肿瘤进展的更高级阶段，而是向另一种组织学形式的转化，就侵袭性而言，这可能包括广泛的癌症。本研究的目的是通过对这两种组织学成分的遗传谱分析，在生物学上对这种病理现象有更多的了解。利用微阵列比较基因组杂交技术，我们比较了8例高级别转化腺样囊性癌常规区和转化区DNA拷贝数的变化，其中4例转化为中分化腺癌，4例转化为低分化腺癌。一般情况下，低分化腺癌患者的拷贝数变化总数高于中分化腺癌患者，这与较差的临床病程相关。特别关注染色体易位和MYB蛋白表达，最近被认为是腺样囊性癌的早期和主要致癌事件。我们的数据表明，高级别转化的过程并不总是伴随着遗传改变的积累；传统的和转化的成分都有独特的基因改变，这表明了一个平行的进展。我们的数据进一步表明，MYB/NFIB易位并不一定是发展为腺样囊性癌并发生高级别转化的早期事件或基础。
Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components. Using microarray comparative genomic hybridization, we compared the genome-wide DNA copy-number changes of the conventional and transformed area of eight adenoid cystic carcinomas with high-grade transformation, comprising four with transformation into moderately differentiated adenocarcinomas and four into poorly differentiated carcinomas. In general, the poorly differentiated carcinoma cases showed a higher total number of copy-number changes than the moderately differentiated adenocarcinonna cases, and this correlated with a worse clinical course. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that the process of high-grade transformation is not always accompanied by an accumulation of genetic alterations; both conventional and transformed components harbored unique genetic alterations, which indicate a parallel progression. Our data further demonstrated that the MYB/NFIB translocation is not necessarily an early event or fundamental for the progression to adenoid cystic carcinoma with high-grade transformation.