Li Zheng Zhe, Kondo Tatsuya, Murata Tomoaki, Ebersole Thomas A, Nishi Toru, Tada Kenji, Ushio Yukitaka, Yamamura Ken-ichi, Abe Kuniya
Department of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan.
Jpn J Cancer Res. 2002 Feb;93(2):167-77. doi: 10.1111/j.1349-7006.2002.tb01255.x.
The quaking gene family encodes single KH domain RNA-binding proteins that play vital roles in cell differentiation, proliferation, and apoptotic processes. The human quaking gene, Hqk, maps to 6q25-q26, where cytogenetic alterations associated with a variety of human malignancies, including gliomas have been reported. To assess possible relationships of Hqk with human diseases such as glial tumors, we first isolated the Hqk gene, characterized its structure and expression pattern, and carried out mutational analysis of Hqk in primary tumor samples. The Hqk gene contains 8 exons spanning a approximately 200 kb genomic region, and generating at least four alternatively spliced transcripts, Hqk-5, Hqk-6, Hqk-7 and Hqk-7B, of which Hqk-7 is abundantly expressed in brain. Analysis of primary tumors demonstrated a high incidence of expression alterations of Hqk in gliomas (30%; 6/20), but not in other tumors such as schwannomas (0/3), or meningiomas (0/8). Among the tumor samples showing expression alterations, two were devoid of all three major transcripts, one was missing only the Hqk-5 message, and only the Hqk-7 message was absent in two cases. Our results thus imply the involvement of Hqk in human glial tumor progression.
震颤基因家族编码具有单个KH结构域的RNA结合蛋白，这些蛋白在细胞分化、增殖和凋亡过程中发挥着至关重要的作用。人类震颤基因Hqk定位于6q25 - q26，据报道该区域的细胞遗传学改变与包括胶质瘤在内的多种人类恶性肿瘤相关。为了评估Hqk与人类疾病如神经胶质瘤之间可能存在的关系，我们首先分离了Hqk基因，对其结构和表达模式进行了表征，并对原发性肿瘤样本中的Hqk进行了突变分析。Hqk基因包含8个外显子，跨越约200 kb的基因组区域，并产生至少四种可变剪接转录本，即Hqk - 5、Hqk - 6、Hqk - 7和Hqk - 7B，其中Hqk - 7在脑中大量表达。对原发性肿瘤的分析表明，Hqk在胶质瘤中的表达改变发生率很高（30%；6/20），但在其他肿瘤如神经鞘瘤（0/3）或脑膜瘤（0/8）中未出现这种情况。在显示表达改变的肿瘤样本中，两个样本缺失了所有三种主要转录本，一个样本仅缺失Hqk - 5信息，还有两个样本仅缺失Hqk - 7信息。因此，我们的结果表明Hqk参与了人类神经胶质瘤的进展。
