ETV6-NTRK3基因融合作为人类分泌性乳腺癌的原发性事件的表达。

Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma.

作者信息

Tognon Cristina, Knezevich Stevan R, Huntsman David, Roskelley Calvin D, Melnyk Natalya, Mathers Joan A, Becker Laurence, Carneiro Fatima, MacPherson Nicol, Horsman Doug, Poremba Christopher, Sorensen Poul H B

机构信息

Department of Pathology & Laboratory Medicine, Children's and Women's Health Centre of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5Z4H4.

出版信息

Cancer Cell. 2002 Nov;2(5):367-76. doi: 10.1016/s1535-6108(02)00180-0.

DOI:10.1016/s1535-6108(02)00180-0

PMID:12450792

Abstract

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.

摘要

我们报告，人类分泌性乳腺癌（SBC）是浸润性导管癌的一种罕见亚型，表达先前在儿童间叶性癌症中克隆的ETV6-NTRK3基因融合体。这种基因融合体编码一种在成纤维细胞中具有强大转化活性的嵌合酪氨酸激酶。在13例SBC病例中的12例（92%）中证实了ETV6-NTRK3的表达，但在其他导管癌中未检测到。将ETV6-NTRK3（EN）逆转录病毒转移到小鼠乳腺上皮细胞中，产生了在裸鼠中易于形成肿瘤的转化细胞。从表型上看，肿瘤形成腺体并表达上皮抗原，证实EN转化与上皮分化相容。这代表了一种反复出现的染色体重排以及一种显性作用癌基因的表达，作为人类乳腺癌的主要事件。