Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma
Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma
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DOI：
10.1016/s1535-6108(02)00180-0
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发表时间：
2002-11-01
期刊：
影响因子：
50.3
通讯作者：
Sorensen, PHB
中科院分区：
文献类型：
--
作者：
Tognon, C;Knezevich, SR;Sorensen, PHB
我们报告说，人类分泌性乳腺癌（SBC）是一种罕见的浸润性导管癌亚型，表达先前在儿科间充质癌中克隆的 ETV6-NTRK3 基因融合体。该基因融合编码一种嵌合酪氨酸激酶，在成纤维细胞中具有有效的转化活性。 ETV6-NTRK3 表达在 13 例 SBC 病例中的 12 例 (92%) 中得到证实，但在其他导管癌中没有表达。 ETV6-NTRK3（EN）逆转录病毒转移到小鼠乳腺上皮细胞中，产生了易于在裸鼠中形成肿瘤的转化细胞。在表型上，肿瘤产生腺体并表达上皮抗原，证实 EN 转化与上皮分化相容。这代表了作为人类乳腺癌主要事件的周期性染色体重排和显性作用癌基因的表达。
We report that human secretory breast carcinoma (SBC), a rare subtype of infiltrating ductal carcinoma, expresses the ETV6-NTRK3 gene fusion previously cloned in pediatric mesenchymal cancers. This gene fusion encodes a chimeric tyrosine kinase with potent transforming activity in fibroblasts. ETV6-NTRK3 expression was confirmed in 12 (92%) of 13 SBC cases, but not in other ductal carcinomas. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed tumors in nude mice. Phenotypically, tumors produced glands and expressed epithelial antigens, confirming that EN transformation is compatible with epithelial differentiation. This represents a recurrent chromosomal rearrangement and expression of a dominantly acting oncogene as a primary event in human breast carcinoma.