THE PROTOONCOGENE CHOP GADD153, INVOLVED IN GROWTH ARREST AND DNA-DAMAGE RESPONSE, IS AMPLIFIED IN A SUBSET OF HUMAN SARCOMAS
THE PROTOONCOGENE CHOP GADD153, INVOLVED IN GROWTH ARREST AND DNA-DAMAGE RESPONSE, IS AMPLIFIED IN A SUBSET OF HUMAN SARCOMAS
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DOI：
10.1016/0165-4608(94)90085-x
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发表时间：
1994-12-01
影响因子：
--
通讯作者：
MYKLEBOST, O
中科院分区：
文献类型：
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作者：
FORUS, A;FLORENES, VA;MYKLEBOST, O
C/EBP同源转录因子CHOP(GADD153)可被生长抑制或DNA损伤诱导，并被证明在人粘液样脂肪肉瘤中被特异性(12；16)易位激活。我们现在已经在两个肉瘤细胞系中发现了CHOP扩增，此前报道了邻近的GLI基因的扩增。在其他98种不同类型的人类肉瘤中，CHOP在一例血管外皮细胞瘤、一例脂肪肉瘤和两例骨肉瘤中扩增。在基因扩增的肿瘤中观察到CHOP的高结构性表达水平，但在其他一些样本中也观察到高水平的CHOP。邻近的MDM2基因编码一种可能使野生型p53失活的蛋白质，此前曾有报道称，该基因在肉瘤中经常被扩增。本组肉瘤中有9例MDM2基因扩增。MDM2和CHOP在其中两个肿瘤中共扩增，而两个骨肉瘤扩增了CHOP，但不扩增MDM2。GLI扩增后，CHOP在两种细胞系中均有扩增，而MDM2仅在一种细胞系中扩增。在MDM2扩增的样本中未发现TP53基因突变。相反，CHOP而不是MDM2扩增的细胞系已经突变了TP53，这表明该扩增子的选择不是通过P53失活来介导的。
The C/EBP-homologous transcription factor CHOP (GADD153) is inducible by growth inhibition or DNA damage, and has been shown to be oncogenically activated by the specific (12;16) translocation in human myxoid liposarcoma. We have now found CHOP amplification in two sarcoma cell lines with previously reported amplification of the nearby GLI gene. Among 98 other human sarcomas of various types, CHOP was amplified in a hemangiopericytoma, a liposarcoma, and two osteosarcomas. High constitutive expression levels of CHOP were observed in tumors with gene amplification, but also in some other samples. The nearby MDM2 gene, which codes for a protein that may inactivate wild-type p53, has previously been reported to be frequently amplified in sarcoma. In our sarcoma panel, MDM2 was amplified in 9 cases. MDM2 and CHOP were co-amplified in two of these, whereas the two osteosarcomas had amplified CHOP but not MDM2. CHOP was amplified in both cell lines with GLI amplification, and MDM2 only in one. No mutations in the TP53 gene have been found in samples with amplification of MDM2. In contrast, the cell line in which CHOP but not MDM2 was amplified had mutated TP53, suggesting that selection of this amplicon was not mediated through p53 inactivation.