Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino Medical School, University of Torino, Medical School Candiolo, Torino, Italy.
PLoS One. 2009 Aug 31;4(8):e6833. doi: 10.1371/journal.pone.0006833.
Frequent somatic mutations have recently been identified in the ras-like domain of the heterotrimeric G protein alpha-subunit (GNAQ) in blue naevi 83%, malignant blue naevi (50%) and ocular melanoma of the uvea (46%). The mutations exclusively affect codon 209 and result in GNAQ constitutive activation which, in turn, acts as a dominant oncogene.
To assess if the mutations are present in other tumor types we performed a systematic mutational profile of the GNAQ exon 5 in a panel of 922 neoplasms, including glioblastoma, gastrointestinal stromal tumors (GIST), acute myeloid leukemia (AML), blue naevi, skin melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, and thyroid carcinomas.
We detected the previously reported mutations in 6/13 (46%) blue naevi. Changes affecting Q209 were not found in any of the other tumors. Our data indicate that the occurrence of GNAQ mutations display a unique pattern being present in a subset of melanocytic tumors but not in malignancies of glial, epithelial and stromal origin analyzed in this study.
最近在异三聚体 G 蛋白 α 亚基（GNAQ）的 ras 样结构域中发现了频繁的体细胞突变，在蓝色痣中占 83%，恶性蓝色痣（50%）和葡萄膜眼部黑色素瘤中占 46%。这些突变仅影响密码子 209，导致 GNAQ 组成性激活，进而充当显性致癌基因。
为了评估这些突变是否存在于其他肿瘤类型中，我们对 922 种肿瘤的 GNAQ 外显子 5 进行了系统的突变分析，包括神经胶质瘤、胃肠道间质瘤（GIST）、急性髓性白血病（AML）、蓝色痣、皮肤黑色素瘤、膀胱癌、乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌和甲状腺癌。
我们在 13 个蓝色痣中的 6 个（46%）中检测到了之前报道的突变。在任何其他肿瘤中都没有发现影响 Q209 的变化。我们的数据表明，GNAQ 突变的发生表现出一种独特的模式，存在于黑素细胞瘤的亚群中，但不存在于本研究中分析的神经胶质、上皮和基质来源的恶性肿瘤中。
