Altered expression and deletion of RM01 in osteosarcoma
Altered expression and deletion of RM01 in osteosarcoma
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DOI：
10.1002/ijc.20786
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发表时间：
2005-05-01
影响因子：
6.4
通讯作者：
Andrulis, IL
中科院分区：
文献类型：
--
作者：
Eppert, K;Wunder, JS;Andrulis, IL
为了增加我们对骨肉瘤进展的分子事件的理解，在24个原发性和转移性骨肉瘤肿瘤标本中检测了大约950个基因的表达。一个基因，RM 01，被分离出来，在转移性样品中表达降低。实时PCR证实了这一模式，揭示了7例原发性和转移性骨肉瘤样本均来自同一患者的病例中有6例的原发性样本中表达较低（p = 0.034）。RM 01位于2 q33，一个在癌症中经常发生杂合性丢失的区域，并且在9个原发性骨肉瘤肿瘤样品中的6个中表现出杂合性丢失（671 c）。在原发性肿瘤中杂合性丢失是明显的，而在转移性样品中观察到基因表达的降低，表明这两个事件分别与癌症进展有关。RM 01的克隆揭示了一个开放的阅读框架，具有多种剪接形式，在含有Pleckstrin同源结构域和Ras关联结构域的区域中与GRB 7、10和14以及MIG 10具有显著的同源性，提示在细胞信号传导和迁移中的作用。北方印迹分析表明RM 01 mRNA在除外周血白细胞外的组织中普遍表达。这些数据表明，RM 01可能是参与抑制肿瘤进展的蛋白质的候选者。(C)2004 Wiley-Liss，Inc.
In order to increase our understanding of the molecular events underlying osteosarcoma progression, the expression of approximately 950 genes was examined in 24 primary and metastatic osteosarcoma tumor specimens. A gene, RM01, was isolated with decreased expression in metastatic samples. Real-Time PCR corroborated this pattern, revealing lower expression in the primary sample in 6 of 7 cases for which both primary and metastatic osteosarcoma samples were available from the same patient (p = 0.034). RM01 is located at 2q33, a region of frequent loss of heterozygosity in cancer, and exhibited loss of heterozygosity in 6 out of 9 primary osteosarcoma tumor samples (671 c). Loss of heterozygosity is evident in primary tumors while the decrease in gene expression is seen in the metastatic samples, indicating that these 2 events are separately implicated in cancer progression. Cloning of RM01 revealed an open reading frame with multiple splice forms with significant homology to GRB7, 10 and 14 and MIG10 in the region containing a Pleckstrin homology domain and a Ras association domain, suggestive of a role in cell signaling and migration. Northern blot analysis indicated that RM01 mRNA is ubiquitously expressed in tissues except for peripheral blood leukocytes. These data suggest that RM01 may be a candidate for a protein involved in inhibiting tumor progression. (C) 2004 Wiley-Liss, Inc.