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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mantle cell lymphoma is characterized by inactivation of the ATM gene
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Mantle cell lymphoma is characterized by inactivation of the ATM gene

机译：套细胞淋巴瘤的特征在于ATM基因失活

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In mantle cell lymphoma (MCL), the translocation t(11:14) is con- sidered the cytogenetic hallmark of the disease. Recently, how- ever, deletion of the chromosomal region 11q22-q23 has been identified as a frequent event in this type of cancer, indicating the existence of a pathogenically relevant tumor suppressor gene in this region. The deleted segment contains the ATM (ataxia telan- giectasia mutated) gene. ATM is an interesting candidate as a tumor suppressor gene because constitutive inactivation of the gene predisposes ataxia telangiectasia patients to lymphoid ma- lignancies. To assess the potential involvement of the gene in MCL lymphomagenesis. we performed mutation analysis of ATM in 12 sporadic cases of MCL. 7 of them with a deletion of one ATM gene copy, by using single-strand conformation polymorphism analysis of reverse transcription--PCR-amplified mRNA and subsequent DNA sequencing. In all seven cases containing a deletion of one ATM allele, a point mutation in the remaining allele was detected, which resulted in aberrant transcript splicing, truncation, or alteration of the protein. In addition. biallelic ATM mutations were identified in two MCLs that did not contain 11 q deletions. Interestingly, in three cases analyzed, the ATM mutations detected in the tumor cells were not present in nonmalignant cells, demonstrating their so- matic rather than germ-line origin. The inactivation of both alleles of the ATM gene by deletion and deleterious point mutation in the majority of cases analyzed indicates that ATM plays a role in the initiation and/or progression of MCL.
机译：在套细胞淋巴瘤（MCL）中，易位t（11:14）被认为是该疾病的细胞遗传学标志。然而，近来，已鉴定出染色体区域11q22-q23的缺失是这种类型的癌症中的常见事件，表明该区域存在致病相关的肿瘤抑制基因。缺失的片段含有ATM（共济失调突变）基因。由于该基因的组成性失活使共济失调性毛细血管扩张症患者易患淋巴结恶性肿瘤，因此ATM作为肿瘤抑制基因是一个有趣的候选者。评估该基因可能参与MCL淋巴瘤的发生。我们对12例散发性MCL病例进行了ATM突变分析。通过使用反转录的单链构象多态性分析-PCR扩增的mRNA和随后的DNA测序，其中7个缺失一个ATM基因拷贝。在所有七个含有一个ATM等位基因缺失的病例中，在其余等位基因中都检测到了点突变，这导致了异常的转录剪接，截短或蛋白改变。此外。在两个不包含11个q缺失的MCL中鉴定出双等位基因ATM突变。有趣的是，在所分析的三例中，在肿瘤细胞中检测到的ATM突变不存在于非恶性细胞中，这表明它们是体细胞来源而不是种系来源。在分析的大多数情况下，通过缺失和有害点突变使ATM基因的两个等位基因失活表明ATM在MCL的发生和/或发展中起作用。

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