Oncogenic mutations in GNAQ occur early in uveal melanoma.
Oncogenic mutations in GNAQ occur early in uveal melanoma.
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DOI：
10.1167/iovs.08-2145
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发表时间：
2008-12
影响因子：
4.4
通讯作者：
Harbour JW
中科院分区：
文献类型：
--
作者：
Onken MD;Worley LA;Long MD;Duan S;Council ML;Bowcock AM;Harbour JW
许多癌症的早期/起始致癌基因突变已被确定，但在葡萄膜黑色素瘤(UM)中仍未发现此类突变。对这类突变进行了广泛的研究，重点放在RAF/MEK/ERK通路上，该通路通常是引发其他类型癌症突变的目标。对来自原发UM的DNA样本进行分析，以检测影响RAF/MEK/ERK通路的24个潜在癌基因的突变。对于最近在葡萄膜黑色素瘤中发现突变的刺激性αQ G蛋白亚基GNAQ，重新测序扩大到包括67个原代细胞和22个外周血样本。分析GNAQ状态与临床、病理、染色体、免疫组织化学和转录特征的关系。在33/67(49%)的原发瘤中发现有209位密码子的激活突变，包括2/9(22%)的虹膜黑色素瘤和31/58(54%)的后发黑瘤。其他23个潜在癌基因均未发现突变。在正常血DNA样本中未发现GNAQ突变。与GNAQ突变是早期或起始事件一致，该突变与任何与晚期肿瘤进展相关的临床、病理或分子特征无关。GNAQ突变发生在大约一半的UM中，代表了这种癌症中最常见的已知致癌突变。在恶性进展的所有阶段的肿瘤中都存在这种突变，这表明这是UM的早期事件。这种G蛋白的突变为UM的发病机制提供了新的见解，并可能带来新的治疗可能性。
Early/initiating oncogenic mutations have been identified for many cancers, but such mutations remain unidentified in uveal melanoma (UM). An extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK pathway, which is often the target of initiating mutations in other types of cancer. DNA samples from primary UMs were analyzed for mutations in 24 potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory αq G-protein subunit which was recently found to be mutated in uveal melanomas, re-sequencing was expanded to include 67 primary UMs and 22 peripheral blood samples. GNAQ status was analyzed for association with clinical, pathologic, chromosomal, immunohistochemical and transcriptional features. Activating mutations at codon 209 were identified in GNAQ in 33/67 (49%) primary UMs, including 2/9 (22%) iris melanomas and 31/58 (54%) posterior UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations were not found in normal blood DNA samples. Consistent with GNAQ mutation being an early or initiating event, this mutation was not associated with any clinical, pathologic or molecular features associated with late tumor progression. GNAQ mutations occur in about half of UMs, representing the most common known oncogenic mutation in this cancer. The presence of this mutation in tumors at all stages of malignant progression suggests that it is an early event in UM. Mutations in this G-protein provide new insights into UM pathogenesis and could lead to new therapeutic possibilities.
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影响因子：
8.8
作者：
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通讯作者：
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