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脑膜瘤中1p32等位基因缺失一致性区域的鉴定:与发病率增加的相关性

Identification of a consistent region of allelic loss on 1p32 in meningiomas: correlation with increased morbidity.

作者信息

Sulman E P, Dumanski J P, White P S, Zhao H, Maris J M, Mathiesen T, Bruder C, Cnaan A, Brodeur G M

机构信息

Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104-4318, USA.

出版信息

Cancer Res. 1998 Aug 1;58(15):3226-30.

PMID:9699646
Abstract

Meningioma is a common tumor of the central nervous system. Deletions of the short arm of chromosome 1 (1p) are the second most commonly observed chromosomal abnormality in these tumors. Here, we analyzed tumor and normal DNAs from 157 meningioma patients using PCR-based polymorphic loci. Loss of heterozygosity (LOH) for at least one informative marker on 1p was observed in 54 cases (34%), whereas LOH on 1q occurred in only 9 cases (8%). High-resolution deletion mapping defined a consensus region of deletion flanked distally by D1S2713 and proximally by D1S2134, which spans 1.5 cM within 1p32. LOH in this region has also been observed in several other malignancies, suggesting the presence of a tumor suppressor gene or genes that are important for several types of cancer. Statistical analysis revealed that 1p LOH was associated with chromosome 22 deletions and with abnormalities of the NF2 gene in meningioma. In addition, unlike other clinical and molecular characteristics, only 1p LOH was shown to be significantly associated with recurrence-free survival.

摘要

脑膜瘤是中枢神经系统的常见肿瘤。1号染色体短臂(1p)缺失是这些肿瘤中第二常见的染色体异常。在此,我们使用基于聚合酶链反应(PCR)的多态性位点分析了157例脑膜瘤患者的肿瘤DNA和正常DNA。在54例(34%)患者中观察到1p上至少一个信息性标记的杂合性缺失(LOH),而1q上的LOH仅发生在9例(8%)患者中。高分辨率缺失图谱确定了一个缺失的共有区域,其远端以D1S2713为界,近端以D1S2134为界,该区域在1p32内跨越1.5厘摩(cM)。在其他几种恶性肿瘤中也观察到该区域的LOH,提示存在对几种类型癌症都很重要的一个或多个肿瘤抑制基因。统计分析显示,脑膜瘤中1p LOH与22号染色体缺失以及NF2基因异常相关。此外,与其他临床和分子特征不同,只有1p LOH显示与无复发生存显著相关。

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