Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas
Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas
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DOI：
10.1002/cncr.21028
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发表时间：
2005-06-01
期刊：
影响因子：
6.2
通讯作者：
Jenkins, RB
中科院分区：
文献类型：
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作者：
Yang, P;Kollmeyer, TM;Jenkins, RB
背景19 q的缺失与神经胶质瘤，特别是少突胶质细胞瘤有关。此外，与没有19 q缺失的病例相比，观察到19 q缺失的少突胶质细胞瘤病例具有更好的生存率。作者先前描述了胶质瘤中的150-腺苷酸酶最小缺失区，该区域定位于19q13.33，包含3个新的候选基因（GLTSCR 1，EHD 2和GLTSCR 2）。作者对141例胶质瘤（61例星形细胞瘤，40例少突胶质细胞瘤，40例混合性少突星形细胞瘤）和108例一般对照进行了关联研究。他们评估了最小19 q缺失区域内和附近的6个基因（ERCC 2，RA 1，ASE-1，ERCC 1，GLTSCR 1和LIG 1）中的7个单核苷酸多态性（SNP）。少突胶质细胞瘤患者生殖系GLTSCR 1外显子1 T等位基因（SNP rs 1035938）的患病率为40%，对照组为27%（P = 0.029），少突胶质细胞瘤患者ERCC 2外显子22 T等位基因（SNP rs 1052555）的患病率为35%，对照组为18%（P = 0.043）。1个高危和1个低危单倍型与少突胶质细胞瘤的发生相关（P值分别为0.003和0.026）。19 q缺失的少突胶质细胞瘤病例与无19 q缺失的病例相比，GLTSCR 1-外显子-1 T等位基因的频率显著更高（P = 0.01）。值得注意的是，GLTSCRI-exon-1 T等位基因纯合的胶质瘤病例的生存率明显更高：2年和5年生存率分别为77%和68%，而其他基因型为56%和34%（P = 0.02，对数秩检验）。多变量分析表明，分级、年龄和GLTSCR 1-外显子1和ERCC 2-外显子22基因型是生存率的独立预测因素。这些结果表明，GLTSCR 1（或一个紧密连锁的基因）的改变与少突胶质细胞瘤的发展和进展。(c)2005年美国癌症协会。
BACKGROUND. Deletions of 19q have been associated with gliomas, especially oligodendrogliomas. In addition, cases with oligodendrogliomas with the 19q deletion have been observed to have a better survival compared with cases without the 19q deletion. The authors have previously described a 150-kilobase minimal deletion region in gliomas that maps to 19q13.33 and contains 3 novel candidate genes (GLTSCR1, EHD2, and GLTSCR2).METHODS. The authors performed an association study using 141 cases with gliomas (61 cases with astrocytomas, 40 cases with oligodendrogliomas, 40 cases with mixed oligoastrocytomas) and 108 general controls. They evaluated 7 single nucleotide polymorphisms (SNPs) in 6 genes within and nearby the minimal 19q deletion region (ERCC2, RA1, ASE-1, ERCC1, GLTSCR1, and LIG1).RESULTS. The prevalence of a germline GLTSCRI-exon-1 T allele (SNP rs1035938) was 40% in cases with oligodendrogliomas compared with 27% in controls (P = 0.029), and the prevalence of an ERCC2-exon-22 T allele (SNP rs1052555) was 35% in cases with oligodendrogliomas compared with 18% in controls (P = 0.043). One high-risk and 1 low-risk haplotype were associated with oligodendroglioma development (P = 0.003 and 0.026, respectively). Cases with oligodendrogliomas with the 19q deletion had a significantly higher frequency of the GLTSCRl-exon-1 T allele compared with cases without the 19q deletion (P = 0.01). It was noteworthy that cases with gliomas who were homozygous for the GLTSCRI-exon-1 T allele had a significantly better survival: 77% and 68% survival at 2 and 5 years compared with 56% and 34% for other genotypes (P = 0.02, log-rank test). Multivariable to analysis identified grade, age, and the GLTSCRI-exon-1 and ERCC2-exon-22 genotypes as independent predictors for survival.CONCLUSIONS. These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of oligoden droglioma. (c) 2005 American Cancer Society.