Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma
Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma
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DOI：
10.1593/neo.06139
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Panagopoulos, Ioannis
中科院分区：
文献类型：
--
作者：
Jin, Yuesheng;Mertens, Fredrik;Panagopoulos, Ioannis
我们的特点是一个平衡的染色体易位t（8;22）（p21;q12）的分子遗传学后果，发生在短期培养的细胞从胸腔内成熟畸胎瘤在一个15岁的女孩的细胞遗传学畸变。荧光原位杂交和逆转录-聚合酶链反应显示t（8;22）导致PPP 2 R2 A和CHEK 2基因的融合，在连接处插入属于I类内源性逆转录病毒相关序列的片段。两个基因的测序没有发现任何额外的突变。检测到的三种PPP 2 R2 A/CHEK 2融合转录物均不产生符合读框的PPP 2 R2 A/CHEK 2嵌合开放阅读框;然而，在所有这些中，CHEK 2的已知开放阅读框被保留。因此，导致CHEK 2表达失调的启动子交换将是最有可能的致癌机制。尽管先前已经在各种散发性肿瘤和遗传性癌症易感综合征中描述了CHEK 2的失活突变，但编码多聚体酶磷酸酶2的调节亚基的PPP 2 R2 A尚未直接参与肿瘤发生。我们的研究结果表明，CHEK 2和/或PPP 2 R2 A的失调是在至少一个子集的生殖细胞肿瘤的发病重要性。
We characterized the molecular genetic consequences of a balanced chromosome translocation t(8;22)(p21;q12), which occurred as the sole cytogenetic aberration in short-term cultured cells from an intrathoracic mature teratoma in a 15-year-old girl. Fluorescence in situ hybridization and reverse transcription-polymerase chain reaction disclosed that t(8;22) resulted in the fusion of the genes PPP2R2A and CHEK2, with an inserted fragment belonging to class I endogenous retrovirus-related sequences at the junction. Sequencing of the two genes did not reveal any additional mutation. None of the three detected PPP2R2A/CHEK2 fusion transcripts resulted in an in-frame PPP2R2A/CHEK2 chimerical open reading frame; however, in all of them, the known open reading frame of CHEK2 was preserved. Thus, promoter swapping leading to deregulated CHEK2 expression would be the most likely oncogenic mechanism. Whereas inactivating mutations of CHEK2 previously have been described in a variety of sporadic tumors and in inherited cancer-predisposing syndromes, PPP2R2A, encoding a regulatory subunit of the multimeric enzyme phosphatase 2, has not been directly implicated in tumorigenesis. Our findings suggest that deregulation of CHEK2 and/or PPP2R2A is of pathogenetic importance in at least a subset of germ cell tumors.