Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas
Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas
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DOI：
10.1016/j.humpath.2005.01.017
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发表时间：
2005-04-01
期刊：
影响因子：
3.3
通讯作者：
Tsuneyoshi, M
中科院分区：
文献类型：
--
作者：
Kawaguchi, K;Oda, Y;Tsuneyoshi, M
PTEN/MMACI（PTEN）基因被鉴定为编码控制细胞过程的细胞质蛋白的肿瘤抑制基因。为探讨PTEN基因在软组织肉瘤（soft tissue sarcomas，STS）中的作用及改变，我们在48例STS中寻找了PTEN基因的纯合性缺失和启动子区高甲基化，包括恶性纤维组织细胞瘤、平滑肌肉瘤、恶性外周神经鞘瘤，其中2例有我们以前报道的突变;差异聚合酶链反应和甲基化特异性聚合酶链反应分别用于分析。此外，为了确定是否PTEN基因的改变参与了PTEN表达的下调，我们检测了38例石蜡包埋组织中PTEN蛋白的表达，其中石蜡包埋组织可用于免疫组化分析。除了我们先前的结果显示51例中有2例（4%）有PTEN突变外，在48例中有6例（13%）发现启动子甲基化，在本研究中，48例中有1例（2%）检测到纯合缺失。6例PTEN基因启动子区甲基化的病例中，5例为恶性周围神经鞘膜瘤。38例STS中11例（29%）PTEN蛋白表达降低。在9例PTEN基因异常的病例中（6例启动子甲基化，2例突变，1例纯合性缺失），3例（33%）PTEN蛋白表达降低。此外，在38例STS病例中，PTEN基因表达降低与高MIB-1标记指数存在统计学显著相关性（P = 0.0441）。总之，启动子甲基化和PTEN基因的纯合性缺失在STS病例中被发现是相对罕见的事件，基因突变也是如此。在9例PTEN基因改变的病例中，3例（33%）显示PTEN表达降低，表明PTEN基因改变似乎在这些肿瘤中的PTEN失活中起次要作用。此外，尽管仍需要对大量病例进行进一步的详细分析，但目前的结果表明，PTEN表达可能是STS患者细胞增殖的有用指标。(c)2005年爱思唯尔公司All rights reserved.
The PTEN/MMACI (PTEN) gene was identified as a tumor suppressor gene encoding a cytoplasmic protein that controls cellular processes. To investigate the potential role and the alteration of the PTEN gene in soft tissue sarcomas (STSs), we searched for homozygous deletion and promoter hypermethylation in a series of 48 STSs that was composed of malignant fibrous histiocytoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, including 2 cases with a mutation that we previously reported; differential polymerase chain reaction and methylation-specific polymerase chain reaction, respectively, were used for the analyses. Furthermore, to determine whether PTEN gene alterations are involved in the down-regulation of PTEN expression, we examined the expression of PTEN protein in 38 cases in which paraffin-embedded tissues were available for immunohistochemical analysis. In addition to our previous results showing that 2 (4%) of 51 cases had a PTEN mutation, promoter methylation was recognized in 6 (13%) of 48 cases, and homozygous deletion was detected in 1 (2%) of 48 cases in the current study. Of 6 cases with promoter methylation of PTEN gene, 5 were malignant peripheral nerve sheath tumor. Decreased expression of PTEN protein was recognized in 11 (29%) of 38 STS cases. Of 9 cases with PTEN alterations (6 cases with promoter methylation, 2 with mutation, and 1 with homozygous deletion), 3 (33%) showed decreased expression of PTEN protein. Furthermore, decreased expression of the PTEN gene showed a statistically significant correlation with high MIB-1 labeling index in 38 STS cases examined (P = .0441). In conclusion, promoter methylation and homozygous deletion of the PTEN gene were found to be relatively rare events in cases of STS, as is mutation of the gene. Of 9 cases with a PTEN alteration, 3 (33%) showed a decrease in PTEN expression, indicating that PTEN gene alterations seem to play a minor role in the inactivation of PTEN in these tumors. Furthermore, although a further detailed analysis of a larger number of cases is still necessary, the present results suggest that PTEN expression may be a useful indicator of cell proliferation in patients with STS. (c) 2005 Elsevier Inc. All rights reserved.