Ladanyi M, Cha C, Lewis R, Jhanwar S C, Huvos A G, Healey J H
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res. 1993 Jan 1;53(1):16-8.
The human homologue of the murine double minute 2 gene (MDM2), a p53-binding protein which may act as a regulator of p53 protein function, has recently been cloned. Initial studies of this gene in a variety of human tumors have shown frequent gene amplification in most types of sarcomas, including osteosarcomas. Amplification of the MDM2 gene may produce a functional inactivation of the p53 protein. To examine possible clinical or pathological correlates of MDM2 gene amplification in osteosarcoma, we studied 28 specimens on 26 patients with high grade osteosarcoma (16 primary, 11 metastatic, and 1 local recurrence) for MDM2 gene amplification by Southern blot analysis, using two MDM2 complementary DNA probes isolated by polymerase chain reaction. Four specimens (14%) showed amplification, including 3 metastases and 1 local recurrence. None of the primary osteosarcoma specimens had detectable MDM2 gene amplification. None of the specimens tested showed MDM2 gene rearrangement. In the present series, MDM2 gene amplification was detected significantly more frequently in metastatic or recurrent osteosarcomas than it was in primary osteosarcomas (P = 0.02). Our data suggest that MDM2 gene amplification may be associated with tumor progression and metastasis in osteosarcoma. Further investigation is warranted on the potential clinicopathological correlates of MDM2 gene amplification in osteosarcoma.
鼠双微体2基因（MDM2）的人类同源基因已被克隆，MDM2是一种p53结合蛋白，可能作为p53蛋白功能的调节因子。最近对该基因在多种人类肿瘤中的初步研究表明，在大多数类型的肉瘤（包括骨肉瘤）中经常出现基因扩增。MDM2基因的扩增可能导致p53蛋白功能失活。为了研究骨肉瘤中MDM2基因扩增可能的临床或病理相关性，我们使用通过聚合酶链反应分离的两种MDM2互补DNA探针，通过Southern印迹分析对26例高级别骨肉瘤患者（16例原发性、11例转移性和1例局部复发病例）的28个标本进行了MDM2基因扩增研究。4个标本（14%）显示扩增，包括3个转移灶和1例局部复发。原发性骨肉瘤标本均未检测到MDM2基因扩增。所检测的标本均未显示MDM2基因重排。在本系列研究中，转移性或复发性骨肉瘤中检测到MDM2基因扩增的频率明显高于原发性骨肉瘤（P = 0.02）。我们的数据表明，MDM2基因扩增可能与骨肉瘤的肿瘤进展和转移有关。有必要进一步研究骨肉瘤中MDM2基因扩增潜在的临床病理相关性。
