MYEOV:: A candidate gene for DNA amplification events occurring centromeric to CCNDI in breast cancer
MYEOV:: A candidate gene for DNA amplification events occurring centromeric to CCNDI in breast cancer
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DOI：
10.1002/ijc.10765
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发表时间：
2002-12-20
影响因子：
6.4
通讯作者：
Theillet, C
中科院分区：
文献类型：
--
作者：
Janssen, JWG;Cuny, M;Theillet, C
人类癌症中经常观察到染色体 11q13 的重排。 11q13 区域包含多个在血液恶性肿瘤中发现的染色体断点簇，并在癌症中表现出频繁的 DNA 扩增。乳腺肿瘤中的 DNA 扩增模式与至少 4 个单独扩增单位的存在一致，表明该区域不止 I 个基因被激活。已鉴定出两个候选癌基因：CCND1 和 EMSI/CORTACTIN，代表集中定位的扩增单元。参与近端和远端扩增子的基因仍有待鉴定。最近我们报道了一个假定的转化基因，MYEOV，将 360 kb 着丝粒定位到 CCND1。发现该基因在 t(11;14)(q13;q32) 阳性多发性骨髓瘤 (MM) 细胞系子集中与 CCND1 一起重排和激活。为了评估 MYEOV 基因在近端扩增核心中的作用，我们测试了 946 个乳腺肿瘤相对于邻近基因或标记物的 MYEOV 拷贝数增加。在 72 个肿瘤子集中研究了 RNA 表达水平，这些肿瘤的 RNA 和 DNA 均可用。这里提供的数据显示，MYEOV 基因在 93% (90/946) 的乳腺肿瘤中扩增，并在 16.6% (12/72) 的乳腺肿瘤中异常表达。扩增模式显示 MYEOV 最常与 CCND1 共扩增 (74/90)，尽管也可以检测到 MYEOV 的独立扩增 (16/90)。异常表达水平仅部分与 DNA 扩增相关。 MYEOV DNA 扩增与雌激素和孕激素受体阳性癌症、浸润性小叶癌类型和腋窝淋巴结受累相关。与 CCND1 扩增相反，未发现与疾病结果的关联。我们的数据表明，MYEOV 是在位于 CCND1 附近的扩增核心中激活的候选癌基因。 (C) 2002 Wilev-Liss, Inc.
Rearrangements of chromosome 11q13 are frequently observed in human cancer. The 11q13 region harbors several chromosomal breakpoint clusters found in hematologic malignancies and exhibits frequent DNA amplification in carcinomas. DNA amplification patterns in breast tumors are consistent with the existence of at least 4 individual amplification units, suggesting the activation of more than I gene in this region. Two candidate oncogenes have been identified, CCND1 and EMSI/CORTACTIN, representing centrally localized amplification units. Genes involved in the proximal and distal amplicons remain to be identified. Recently we reported on a putative transforming gene, MYEOV, mapping 360 kb centromeric to CCND1. This gene was found to be rearranged and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32)-positive multiple myeloma (MM) cell lines. To evaluate the role of the MYEOV gene in the proximal amplification core, we tested 946 breast tumors for copy number increase of MYEOV relative to neighboring genes or markers. RNA expression levels were studied in a subset of 72 tumors for which both RNA and DNA were available. Data presented here show that the MYEOV gene is amplified in 93% (90/946) and abnormally expressed in 16.6% (12/72) of breast tumors. Amplification patterns showed that MYEOV was most frequently coamplified with CCND1 (74/90), although independent amplification of MYEOV could also be detected (16/90). Abnormal expression levels correlated only partially with DNA amplification. MYEOV DNA amplification correlated with estrogen and progesterone receptor-positive cancer, invasive lobular carcinoma type and axillary nodal involvement. In contrast to CCND1 amplification, no association with disease outcome could be found. Our data suggest that MYEOV is a candidate oncogene activated in the amplification core located proximal to CCND1. (C) 2002 Wilev-Liss, Inc.