Pageau Gayle J, Hall Lisa L, Ganesan Shridar, Livingston David M, Lawrence Jeanne B
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Nat Rev Cancer. 2007 Aug;7(8):628-33. doi: 10.1038/nrc2172. Epub 2007 Jul 5.
Interest has recently reawakened in whether loss of the heterochromatic X chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and new insights into the mechanisms involved have emerged. Mitotic segregation errors commonly explain the loss of the inactive X chromosome (Xi), but compromise of Xi heterochromatin in some cancers may signal broader deficits of nuclear heterochromatin. The debated link between BRCA1 and Xi might reflect a general relationship between BRCA1 and heterochromatin, which could connect BRCA1 to both epigenetic and genetic instability. We suggest that heterochromatic instability is a common but largely unexplored mechanism, leading to widespread genomic misregulation and the evolution of some cancers.
最近,人们重新开始关注异染色质X染色体(巴氏小体)的缺失在某些乳腺癌和卵巢癌中是否普遍存在,并且对其中涉及的机制有了新的认识。有丝分裂分离错误通常可以解释失活X染色体(Xi)的丢失,但在某些癌症中Xi异染色质的受损可能预示着核异染色质存在更广泛的缺陷。BRCA1与Xi之间存在争议的联系可能反映了BRCA1与异染色质之间的普遍关系,这可能将BRCA1与表观遗传和基因不稳定联系起来。我们认为,异染色质不稳定是一种常见但很大程度上未被探索的机制,会导致广泛的基因组调控异常以及某些癌症的演变。