Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
J Clin Invest. 2012 Aug;122(8):2983-8. doi: 10.1172/JCI64400. Epub 2012 Jul 17.
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.
癌症主要被认为是一种遗传疾病，许多突变被认为对其生长至关重要。然而，存在基因组稳定的癌症以及编码染色质重塑因子的基因突变的出现，提出了这样一种可能性，即染色质结构和表观遗传调控的扰动能够驱动癌症的形成。在这里，我们对 35 例横纹肌瘤进行了外显子组测序，横纹肌瘤是一种高度侵袭性的儿童早期癌症，其特征是 SWI/SNF 染色质重塑复合物的一个亚基 SMARCB1 的双等位基因缺失。我们发现突变率极低，SMARCB1 的缺失基本上是唯一的反复出现的事件。事实上，在 2 例癌症中没有发现其他的基因突变。我们的结果表明，对于由染色质重塑复合物突变驱动的癌症的发生，高突变率是可有可无的。因此，癌症可以是一种具有显著遗传简单性的疾病。
