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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck
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Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck

机译：MYB和NFIB转录因子基因在乳腺癌和头颈癌中的复发融合

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摘要

The transcription factor gene MYB was identified recently as an oncogene that is rearranged/duplicated in some human leukemias. Here we describe a new mechanism of activation of MYB in human cancer involving gene fusion. We show that the t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinomas (ACC) of the breast and head and neck consistently results in fusions encoding chimeric transcripts predominantly consisting of MYB exon 14 linked to the last coding exon(s) of NFIB. The minimal common part of MYB deleted as the result of fusion was exon 15 including the 3'-UTR, which contains several highly conserved target sites for miR-15a/16 and miR-150 microRNAs. These microRNAs recently were shown to regulate MYB expression negatively. We suggest that deletion of these target sites may disrupt repression of MYB leading to overexpression of MYB-NFIB transcripts and protein and to activation of critical MYB targets, including genes associated with apoptosis, cell cycle control, cell growth/angiogenesis, and cell adhesion. Forced overexpression of miR-15a/16 and miR-150 in primary fusion-positive ACC cells did not significantly alter the expression of MYB as compared with leukemic cells with MYB activation/duplication. Our data indicate that the MYB-NFIB fusion is a hallmark of ACC and that deregulation of the expression of MYB and its target genes is a key oncogenic event in the pathogenesis of ACC. Our findings also suggest that the gain-of-function activity resulting from the MYB-NFIB fusion is a candidate therapeutic target.
机译：转录因子基因MYB最近被鉴定为在某些人类白血病中重排/复制的癌基因。在这里，我们描述了涉及基因融合的人类癌症中MYB激活的新机制。我们显示t（6; 9）（q22-23; p23-24）在乳房和头颈部腺样囊性癌（ACC）中的易位始终导致融合的编码主要由MYB外显子14组成的嵌合转录本的融合体NFIB的最后一个编码外显子。由于融合而缺失的MYB的最小共同部分是外显子15，包括3'-UTR，该外显子包含几个miR-15a / 16和miR-150 microRNA高度保守的靶位点。这些微RNA最近显示负调节MYB表达。我们建议删除这些靶位点可能会破坏MYB的阻遏，导致MYB-NFIB转录本和蛋白质的过度表达以及关键MYB靶的激活，包括与凋亡，细胞周期控制，细胞生长/血管生成和细胞粘附相关的基因。与具有MYB激活/复制功能的白血病细胞相比，在原发性融合阳性ACC细胞中miR-15a / 16和miR-150的强迫过表达不会显着改变MYB的表达。我们的数据表明，MYB-NFIB融合体是ACC的标志，而MYB及其靶基因表达的失调是ACC发病机理中的关键致癌事件。我们的发现还表明，由MYB-NFIB融合产生的功能获得活性是候选治疗靶标。

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    Marta Persson; Ywonne Andren; Joachim Mark; Hugo M. Horlings; Fredrik Persson; Goeran Stenman;

  • 作者单位

    Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;

    Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;

    Department of Pathology, Central Hospital, SE-541 85 Skovde, Sweden;

    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066CX, Amsterdam, The Netherlands;

    Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;

    Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden Department of Pathology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    chromosome translocation; fusion oncogene; miRNA; adenoid cystic carcinoma;

    机译：染色体易位融合癌基因miRNA;腺样囊性癌;

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