Impact of novel PTEN mutations in Turkish patients with glioblastoma multiforme
Impact of novel PTEN mutations in Turkish patients with glioblastoma multiforme
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DOI：
10.1007/s11060-006-9293-z
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发表时间：
2007-05-01
影响因子：
3.9
通讯作者：
Aksoy, Kaya
中科院分区：
文献类型：
--
作者：
Tunca, Berrin;Bekar, Ahmet;Aksoy, Kaya
多形性胶质母细胞瘤（GBM）是中枢神经系统最常见和最具侵袭性的原发性肿瘤。PTEN（磷酸酶，张力蛋白同源物，在染色体TEN上缺失; MIM # 601728）肿瘤抑制基因在胶质母细胞瘤的形成中具有重要的生物学作用。众所周知，在不同种族背景的患者中发生的肿瘤遗传改变存在差异，并且由于没有研究评估土耳其GBM患者中的PTEN突变，我们旨在实现本研究。我们采用单链构象多态性（SSCP）方法和DNA测序技术对62例GBM肿瘤进行了PTEN基因突变的研究。我们的研究结果显示，62例肿瘤中有15例（24.19%）检测到PTEN突变。鉴定了九种不同的序列变体：一个新的启动子位点突变（5' UTR -9 C-> T），一个新的内含子突变（IVS 2 -2delA），四个新的点突变（61A -> G、105T -> G、248C -> G和364C -> G），两个新的移码突变（213 delC）和378 delGATA）和一个先前报道的全外显子转换型突变（129 G-> A）。由于本研究中发现的大多数PTEN突变是新的，我们认为这些改变可能是土耳其人群特有的。此外，虽然没有显着的相关性，发现之间的PTEN突变和GBM肿瘤的组织病理学特性，我们的研究结果表明，在PTEN基因突变的本地化可能有影响GBM肿瘤的临床侵袭性。
Glioblastoma multiforme (GBM) represents the most common and aggressive type of primary neoplasms of the central nervous system. The PTEN ( phosphatase, tensin homologue, deleted on chromosome TEN; MIM # 601728) tumor suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in tumors that develop in patients with different ethnic backgrounds and because there is no study evaluating PTEN mutation in Turkish patients with GBM, we aimed to realize the present study. We investigated 62 GBM tumors for mutations of the PTEN gene using single strand conformational polymorphism ( SSCP) method followed by DNA sequencing. As a result of our investigation, PTEN mutations were detected in 15 of 62 tumors (24.19%). Nine different sequence variants were identified: one novel promoter site mutation ( 5' UTR - 9C -> T), one novel intronic mutation (IVS2-2delA), four novel point mutations (61A -> G, 105T -> G, 248C -> G, and 364C -> G), two novel frameshift mutations (213delC) and 378delGATA) and one previously reported global exonic transition type mutation ( 129G -> A). Since the majority of PTEN mutations identified in the present study are novel, we believe that these alterations may be specific to Turkish population. Furthermore, though no significant correlation was found between PTEN mutations and histopathological properties of GBM tumors, our findings indicate that localizations of mutations in PTEN gene may have an effect on clinical aggressiveness of GBM tumors.