Microsatellite deletion mapping on chromosome 10q and mutation analysis of MMAC1, FAS, and MXI1 in human glioblastoma multiforme.
Microsatellite deletion mapping on chromosome 10q and mutation analysis of MMAC1, FAS, and MXI1 in human glioblastoma multiforme.
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DOI：
10.3892/ijo.12.4.905
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发表时间：
1998-04
影响因子：
5.2
通讯作者：
D. Fults;C. Pedone;G. Thompson;C. Uchiyama;K. Gumpper;D. Iliev;V. L. Vinson;S. Tavtigian;W. Perry
中科院分区：
文献类型：
--
作者：
D. Fults;C. Pedone;G. Thompson;C. Uchiyama;K. Gumpper;D. Iliev;V. L. Vinson;S. Tavtigian;W. Perry
多形性胶质母细胞瘤（GBM）是一种终末期胶质源性脑肿瘤。GBM中经常发生包含染色体10 q全部或部分的等位基因缺失，表明10 q上一个或多个肿瘤抑制基因的缺失在GBM形成中起作用。这些基因之一是MMAC1（PTEN），10q23上的基因，其编码双特异性蛋白磷酸酶。我们对66例GBM患者进行了10 q上27个微卫星标记的杂合性丢失（洛）分析。总的来说，在70%的病例中检测到洛缺失，大多数病例显示每个信息标记都存在洛缺失。11例患者显示部分10q缺失，最小的跨越D10S187远端的35 cM区域。45例肿瘤中的MMAC 1基因序列分析显示11例（24%）发生突变，均在10 q上发生洛缺失。这些突变都不存在于同一患者的正常DNA中。此外，我们利用SSCP分析测试10 q上的另外两个候选基因：FAS，一种转导凋亡、细胞死亡信号的细胞表面受体和MXI 1，一种转录抑制因子。这些基因中没有突变表明FAS和MXI 1不太可能是与GBM生理相关的肿瘤抑制基因。这些数据确实支持MMAC 1在GBM中发挥重要作用。
Glioblastoma multiforme (GBM) is an end-stage brain tumor of glial origin. Allelic deletions encompassing all or part of chromosome 10q occur frequently in GBMs, indicating that loss of one or more tumor suppressor genes on 10q plays a role in GBM formation. One of these genes is MMAC1 (PTEN), a gene on 10q23 which encodes a dual-specificity protein phosphatase. We carried out a loss of heterozygosity (LOH) analysis of 66 GBM patients using microsatellite markers for 27 loci on 10q. Overall, LOH was detected in 70% of cases, most showing LOH with every informative marker. Eleven patients showed partial 10q deletions, the smallest spanning a 35 cM region distal to D10S187. Sequence analysis of the MMAC1 gene in 45 of these tumors revealed mutations in eleven cases (24%), all with LOH on 10q. None of these mutations was present in normal DNA from the same patients. In addition, we utilized SSCP analysis to test two other candidate genes on 10q: FAS, a cell surface receptor which transduces an apoptotic, cell death signal and MXI1, a transcriptional repressor. The absence of mutations in these genes suggested that FAS and MXI1 are not likely to be tumor suppressor genes physiologically relevant to GBM. These data do support a significant role for MMAC1 in GBM.