Sahlgrenska Cancer Center, Department of Pathology, Sahlgrenska Academy at University of Gothenburg, Sweden.
J Pathol. 2011 Jul;224(3):322-7. doi: 10.1002/path.2909. Epub 2011 May 27.
We have recently shown that the recurrent t(6;9)(q22 ∼ 23;p23 ∼ 24) translocation in adenoid cystic carcinoma (ACC) of the breast and head and neck results in a fusion of the two transcription factor genes MYB and NFIB. Here we demonstrate, for the first time, that benign sporadic, dermal cylindromas also express the MYB-NFIB gene fusion. RT-PCR and immunohistochemical analyses revealed that eight of 12 analysed tumours (67%) expressed MYB-NFIB fusion transcripts and/or stained positive for MYB protein. Nucleotide sequence analyses confirmed that the composition of the chimeric transcript variants identified was identical to that in ACC, suggesting a similar molecular mechanism of activation of MYB in cylindroma as in ACC. In contrast, no evidence for the presence of the MYB-NFIB fusion was found in other types of basaloid skin and salivary gland tumours, indicating that the fusion indeed has a restricted expression pattern. Our findings broaden the spectrum of neoplasms associated with MYB oncogene activation and reveal a novel genetic link between ACC and dermal cylindroma. These results, together with our previous observations, further strengthen the evidence for common molecular pathways of importance for the development of both benign and malignant breast, salivary and adnexal tumours.
我们最近发现，乳腺和头颈部腺样囊性癌（ACC）中反复出现的 t(6;9)(q22∼23;p23∼24)易位导致两个转录因子基因 MYB 和 NFIB 融合。在这里，我们首次证明良性散发性皮肤圆柱瘤也表达 MYB-NFIB 基因融合。RT-PCR 和免疫组织化学分析显示，在分析的 12 个肿瘤中的 8 个（67%）表达 MYB-NFIB 融合转录本和/或 MYB 蛋白阳性染色。核苷酸序列分析证实，鉴定的嵌合转录变体的组成与 ACC 中的相同，提示 MYB 在圆柱瘤中的激活与 ACC 中具有相似的分子机制。相比之下，在其他基底细胞样皮肤和唾液腺肿瘤中未发现 MYB-NFIB 融合的存在，表明该融合确实具有受限的表达模式。我们的发现拓宽了与 MYB 癌基因激活相关的肿瘤谱，并揭示了 ACC 和皮肤圆柱瘤之间的新的遗传联系。这些结果，连同我们之前的观察结果，进一步证实了对良性和恶性乳腺、唾液腺和附属器肿瘤的发展具有重要意义的共同分子途径的证据。
