Liang B C, Ross D A, Reed E
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J Neurooncol. 1995 Oct;26(1):17-23. doi: 10.1007/BF01054765.
Abnormalities of the genomic region of chromosome 19q13.2-13.4 are a common occurrence in brain malignancies and contain a possible tumor suppressor gene involved in gliomas. Since abnormalities of DNA repair are associated with malignancy, we assessed DNA status of the nucleotide excision repair genes located in this area, viz. ERCC1 and ERCC2. Radiodensitometry was used to assess gene copy number in samples obtained from brain tumor specimens from 24 patients. Nine tumors were of lower grade histology (3 pilocytic astrocytomas, 2 gangliogliomas, 4 astrocytomas); 15 tumors were pathologically higher grade (4 anaplastic astrocytomas, 11 glioblastomas). Tumor samples were obtained prior to radiation or chemotherapy. Abnormalities of gene copy number of ERCC1 and ERCC2 were observed in 11/24 specimens (46%). Whereas increased and decreased copy numbers were observed for ERCC1, only decreases in copy number of ERCC2 were seen. Three tumors (all lower grade) showed concurrent allelic loss of ERCC1 and ERCC2. Abnormalities of copy number for these genes were not associated with response to subsequent therapy nor survival. However, allelic loss of ERCC2 was associated with younger age at diagnosis when compared to those specimens which did not show loss. There were no significant differences between lower grade and higher grade tumors with respect to these investigations. Abnormalities in copy number of ERCC1 and ERCC2 are common in glial tumors. Further study of this genomic region is necessary to define the importance of these observations in tumor pathophysiology and treatment.
19号染色体19q13.2 - 13.4区域的基因组异常在脑恶性肿瘤中很常见，该区域包含一个可能与胶质瘤相关的肿瘤抑制基因。由于DNA修复异常与恶性肿瘤有关，我们评估了位于该区域的核苷酸切除修复基因（即ERCC1和ERCC2）的DNA状态。采用放射密度测定法评估从24例患者的脑肿瘤标本中获取的样本中的基因拷贝数。9个肿瘤为低级别组织学类型（3个毛细胞型星形细胞瘤、2个节细胞胶质瘤、4个星形细胞瘤）；15个肿瘤病理级别较高（4个间变性星形细胞瘤、11个胶质母细胞瘤）。肿瘤样本在放疗或化疗之前获取。在11/24个标本（46%）中观察到ERCC1和ERCC2基因拷贝数异常。ERCC1观察到拷贝数增加和减少，而ERCC2仅观察到拷贝数减少。3个肿瘤（均为低级别）显示ERCC1和ERCC2同时发生等位基因缺失。这些基因的拷贝数异常与后续治疗反应或生存率无关。然而，与未显示缺失的标本相比，ERCC2的等位基因缺失与诊断时年龄较小有关。在这些研究方面，低级别和高级别肿瘤之间没有显著差异。ERCC1和ERCC2的拷贝数异常在胶质肿瘤中很常见。有必要对该基因组区域进行进一步研究，以确定这些观察结果在肿瘤病理生理学和治疗中的重要性。
