Jeng Yung-Ming, Hsu Hey-Chi
Department of Pathology, National Taiwan University Hospital, No. 7 Chung-Shan Road, Taipei 100, Taiwan.
Int J Cancer. 2003 Jul 10;105(5):625-9. doi: 10.1002/ijc.11123.
Gliomas are the most common tumors of the central nervous system and have a grave prognosis. Deletion of chromosome 10p15 is one of the most common chromosomal alterations in gliomas. Recently, a candidate tumor suppressor gene, KLF6, which is mapped to chromosome 10p, was found to be frequently mutated in prostate cancer. KLF6 is a zinc finger transcription factor and transactivates p21/WAF1/CIP expression. To elucidate the role of genetic alterations of KLF6 in gliomas, we analyzed the 4 exons of the gene by direct DNA sequencing in 155 gliomas. Of these, mutations of KLF6 were found in 9 of 76 (11.8%) glioblastomas multiforme, 2 of 28 (7.1%) anaplastic astrocytomas, 2 of 36 (5.5%) low-grade diffuse astrocytomas and in none of the 15 oligodendrogliomas. All 13 mutations were located in the transactivation domain and most of them affected either serine residues or codons next to serine residues. Of the 13 cases with KLF6 mutation, loss of heterozygosity (LOH) at the KLF6 locus was inferred from the LOH displayed by the flanking microsatellite markers in 11 cases. We conclude that mutations of the KLF6 gene play a role in the pathogenesis of astrocytic gliomas.
神经胶质瘤是中枢神经系统最常见的肿瘤，预后严重。10p15染色体缺失是神经胶质瘤中最常见的染色体改变之一。最近，一个定位于10号染色体的候选抑癌基因KLF6被发现经常在前列腺癌中发生突变。KLF6是一种锌指转录因子，可反式激活p21/WAF1/CIP的表达。为了阐明KLF6基因改变在神经胶质瘤中的作用，我们通过直接DNA测序分析了155例神经胶质瘤中该基因的4个外显子。其中，在76例多形性胶质母细胞瘤中有9例（11.8%）发现KLF6突变，28例间变性星形细胞瘤中有2例（7.1%），36例低级别弥漫性星形细胞瘤中有2例（5.5%），而15例少突胶质细胞瘤中均未发现。所有13个突变均位于反式激活结构域，且大多数影响丝氨酸残基或丝氨酸残基旁的密码子。在13例KLF6突变的病例中，11例通过侧翼微卫星标记显示的杂合性缺失（LOH）推断出KLF6基因座存在杂合性缺失。我们得出结论，KLF6基因的突变在星形细胞神经胶质瘤的发病机制中起作用。
