人类胶质瘤复发时10号染色体等位基因丢失的积累。

K Tokiyoshi, T Yoshimine, M Maruno, A K Muhammad, T Hayakawa
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引用次数: 9

摘要

目的:阐明10号染色体等位基因丢失在人类胶质瘤恶性进展中的意义。方法:分析8个微卫星位点(D10S249、D10S191、D10S210、D10S219、D10S246、D10S222、D10S221和D10S212)在组织学上良性和恶性的染色体缺失,包括复发性胶质瘤。在16例原发肿瘤(2例星形细胞瘤,9例间变性星形细胞瘤和5例胶质母细胞瘤)中,复发时的组织学诊断为间变性星形细胞瘤6例,胶质母细胞瘤10例。从福尔马林固定、石蜡包埋的切片中提取基因组DNA。原始肿瘤和复发肿瘤的样本配对并使用PCR扩增。组织学正常的大脑样本作为对照。结果:在原发肿瘤中,所有5例胶质母细胞瘤、9例间变性星形细胞瘤中的5例(56%)和所有星形细胞瘤均表现为10号染色体杂合性缺失。在5例复发后进展为胶质母细胞瘤的间变性星形细胞瘤中检测到额外的LOH。在2例复发后发展为间变性星形细胞瘤的星形细胞瘤中未检测到额外的LOH。除1例外,在复发性胶质母细胞瘤中观察到额外的LOH。结论在相邻的两个微卫星标记D10S222和D10S221位点(10q23-q25)观察到- loh,提示10号染色体上的这一区域与间变性星形细胞瘤向胶质母细胞瘤的发展密切相关。
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Accumulation of allelic losses on chromosome 10 in human gliomas at recurrence.

Aims-To elucidate the implications of allelic loss on chromosome 10 in the malignant progression of human gliomas.Methods-Eight microsatellite loci (D10S249, D10S191, D10S210, D10S219, D10S246, D10S222, D10S221, and D10S212) were analysed for chromosomal deletions in histologically benign and malignant, including recurrent, gliomas. Of the 16 original tumours studied (two astrocytomas, nine anaplastic astrocytomas and five glioblastomas), the histological diagnosis at recurrence was anaplastic astrocytoma in six cases and glioblastoma in 10. Genomic DNA was extracted from formalin fixed, paraffin wax embedded sections. Samples of original and recurrent tumours were paired and amplified using PCR. Samples of histologically normal brain served as controls.Results-Of the original tumours, all five glioblastomas, five (56%) of nine anaplastic astrocytomas and none of the astrocytomas demonstrated loss of heterozygosity (LOH) on chromosome 10. Additional LOH was detected in the five cases of anaplastic astrocytoma that progressed to glioblastoma at recurrence. Additional LOH was not detected in the two cases of astrocytoma that progressed to anaplastic astrocytoma at recurrence. With the exception of one case, additional LOH was observed in the recurrent glioblastomas.Conclusion-LOH was observed at the loci of two adjacent microsatellite markers, D10S222 and D10S221 (10q23-q25), suggesting that this region on chromosome 10 is closely related to progression from anaplastic astrocytoma to glioblastoma.

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