A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers
A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers
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DOI：
10.1172/jci64400
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发表时间：
2012-08-01
影响因子：
15.9
通讯作者：
Roberts, Charles W. M.
中科院分区：
文献类型：
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作者：
Lee, Ryan S.;Stewart, Chip;Roberts, Charles W. M.
癌症主要被认为是一种遗传疾病，许多突变被认为是驱动其生长的关键。然而，基因组稳定的癌症的存在和编码染色质重塑的基因突变的出现提高了染色质结构和表观遗传调控的扰动能够驱动癌症形成的可能性。在这里，我们对35个横纹肌样肿瘤的外显子组进行了测序，横纹肌样肿瘤是一种高度侵袭性的儿童早期癌症，其特征是SMARCB 1的双等位基因缺失，SMARCB 1是SWI/SNF染色质重塑复合物的一个亚基。我们发现了一个极低的突变率，SMARCB 1的丢失基本上是唯一的复发事件。事实上，在2种癌症中没有发现其他突变。我们的研究结果表明，高突变率是由染色质重塑复合物突变驱动的癌症发生的关键。因此，癌症可能是一种非常简单的遗传疾病。
Cancer is principally considered a genetic disease, and numerous mutations are thought essential to drive its growth. However, the existence of genomically stable cancers and the emergence of mutations in genes that encode chromatin remodelers raise the possibility that perturbation of chromatin structure and epigenetic regulation are capable of driving cancer formation. Here we sequenced the exomes of 35 rhabdoid tumors, highly aggressive cancers of early childhood characterized by biallelic loss of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. We identified an extremely low rate of mutation, with loss of SMARCB1 being essentially the sole recurrent event. Indeed, in 2 of the cancers there were no other identified mutations. Our results demonstrate that high mutation rates are dispensable for the genesis of cancers driven by mutation of a chromatin remodeling complex. Consequently, cancer can be a remarkably genetically simple disease.