Activating GNAS Mutations in Parosteal Osteosarcoma
Activating GNAS Mutations in Parosteal Osteosarcoma
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DOI：
10.1097/pas.0000000000000144
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发表时间：
2014-03-01
影响因子：
5.6
通讯作者：
Fritchie, Karen J.
中科院分区：
文献类型：
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作者：
Carter, Jodi M.;Inwards, Carrie Y.;Fritchie, Karen J.
骨旁骨肉瘤是一种以表面为基础的骨肉瘤，通常表现出虚假的平淡无奇的细胞学特征，阻碍了小活检的诊断或相关的放射成像不容易获得。许多良性和恶性的纤维骨性病变，包括纤维异常增殖症(FD)和低度恶性中央型骨肉瘤，都属于骨旁骨肉瘤的形态鉴别诊断。编码异三聚体G蛋白复合体(Gsα)α亚单位的GNAS的体细胞突变在FD和McCune-Albright综合征中发生，但在骨旁骨肉瘤中尚未见报道。我们评估了骨旁骨肉瘤的GNAS突变状态及其几个组织学模拟，以确定其在区分这些实体方面的有效性。14例FD中有11例(79%)存在201密码子的GNAS突变(5例R201C突变和6例R201H突变)。在任何牙釉质瘤或骨纤维异常增生症病例中均未检测到GNAS突变。对9例骨旁骨肉瘤进行直接测序，发现5例(55%)存在GNAS基因突变，其中4例为R201C突变，1例为R201H突变。在所有病例中均未检测到GNAS密码子227突变。GNAS突变状态与患者的人口学特征、组织学去分化或临床结果之间没有关联。据我们所知，我们报道了第一系列含有激活GNAS突变的骨旁骨肉瘤。我们的数据表明，GNAS突变状态作为鉴别骨良恶性纤维骨性病变的辅助技术的作用可能有限。
Parosteal osteosarcoma is a surface-based osteosarcoma that often exhibits deceptively bland cytologic features, hindering diagnosis in small biopsies or when correlative radiologic imaging is not readily available. A number of benign and malignant fibro-osseous lesions, including fibrous dysplasia (FD) and low-grade central osteosarcoma, fall within the morphologic differential diagnosis of parosteal osteosarcoma. Somatic mutations in GNAS, encoding the alpha-subunit of the heterotrimeric G protein complex (Gs alpha), occur in FD and McCune-Albright syndrome but have not been reported in parosteal osteosarcoma. We evaluated GNAS mutational status in parosteal osteosarcoma and several of its histologic mimics to determine its utility in differentiating these entities. Eleven of 14 (79%) FD cases had GNAS mutations within codon 201 (5 R201C and 6 R201H mutations). GNAS mutations were not detected in any cases of adamantinoma or osteofibrous dysplasia. Direct sequencing of 9 parosteal osteosarcomas, including 3 of low grade and 6 with dedifferentiation, revealed activating GNAS mutations in 5 cases (55%), distributed as 4 R201C-mutated tumors and 1 tumor with an R201H mutation. GNAS codon 227 mutations were not detected in any of the cases. There was no association between GNAS mutational status and patient demographics, histologic dedifferentiation, or clinical outcome. To our knowledge, we report the first series of parosteal osteosarcomas harboring activating GNAS mutations. Our data suggest that GNAS mutational status may have limited utility as an ancillary technique in differentiating benign and malignant fibro-osseous lesions of the bone.