Hulsebos T J M, Troost D, Leenstra S
Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
J Neurol Neurosurg Psychiatry. 2004 May;75(5):723-6. doi: 10.1136/jnnp.2003.025031.
Due to their invasive growth, gliomas usually cannot be removed completely and almost always recur as same grade or higher grade malignancies.
To determine whether there were differences in the accumulation of genetic changes between the two types of glioma recurrence.
We genetically characterised 14 cases of lower grade glioma with a same grade recurrence, 12 cases of glioblastoma recurrence, and 14 cases of lower grade glioma with a higher grade recurrence. We investigated LOH (loss of heterozygosity) at 1p36, 10p15, the PTEN region in 10q23, the DMBT1 region in 10q25, 19q13, 22q13, LOH and mutation of TP53, and EGFR amplification.
Genetic heterogeneity in the primary tumour was inferred in 3 cases of lower grade glioma with a higher grade recurrence. The cases of lower grade glioma with a higher grade recurrence displayed increased genetic instability in the recurrence (mean of 2.0 additional genetic changes per case) compared to cases with a same lower grade recurrence or those with a glioblastoma recurrence (mean of 0.6 and 0.8 additional changes per case, respectively). Compared to unselected primary glioblastomas, the glioblastomas that recurred as an operable tumour had infrequent EGFR amplification (8% v 30-40% of cases).
Gliomas recurring as higher grade lesions might be genetically heterogeneous and accumulate more genetic changes than gliomas recurring as same grade lesions (whether originally low or high grade). Primary glioblastomas from patients for which the recurrence is operated because of prognostically more favourable clinical indices have infrequent EGFR amplification.
由于胶质瘤呈浸润性生长，通常无法完全切除，几乎总会复发为相同级别或更高级别的恶性肿瘤。
确定两种类型的胶质瘤复发在基因改变积累方面是否存在差异。
我们对14例低级别胶质瘤同级别复发、12例胶质母细胞瘤复发以及14例低级别胶质瘤高级别复发的病例进行了基因特征分析。我们研究了1p36、10p15、10q23的PTEN区域、10q25的DMBT1区域、19q13、22q13的杂合性缺失（LOH），TP53的LOH和突变，以及EGFR扩增情况。
在3例低级别胶质瘤高级别复发病例中推断出原发肿瘤存在基因异质性。与低级别胶质瘤同级别复发或胶质母细胞瘤复发的病例相比（分别为每例平均额外有0.6个和0.8个基因改变），低级别胶质瘤高级别复发的病例在复发时显示出基因不稳定性增加（每例平均额外有2.0个基因改变）。与未选择的原发性胶质母细胞瘤相比，复发时为可手术切除肿瘤的胶质母细胞瘤EGFR扩增较少（8%对30 - 40%的病例）。
复发为更高级别病变的胶质瘤可能在基因上具有异质性，并且比复发为相同级别病变的胶质瘤（无论最初是低级别还是高级别）积累更多的基因改变。因临床指标预后更有利而接受手术复发治疗的患者的原发性胶质母细胞瘤EGFR扩增较少。
