Visser M, Bras J, Sijmons C, Devilee P, Wijnaendts L C, van der Linden J C, Voûte P A, Baas F
Neurozintuigen Laboratory, Emma Kinderziekenhuis, Academic Medical Center, Amsterdam, The Netherlands.
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9172-6. doi: 10.1073/pnas.93.17.9172.
Replication errors (RERs) were initially identified in hereditary nonpolyposis colon cancer and other tumors of Lynch syndrome II. Mutations in genes involved in mismatch repair give rise to a mutator phenotype, resulting in RERs. The mutator phenotype is thought to predispose to malignant transformation. Here we show that in the embryonal form of childhood rhabdomyosarcoma, RERs also occur, but in contrast to hereditary nonpolyposis colon cancer, only a subset of the microsatellite loci analyzed show RERs. The occurrence of RERs is strongly correlated with increased fractional allelic loss (P < 0.001), suggesting that the occurrence of RERs is a secondary phenomenon in rhabdomyosarcoma. Coincidental loss of genes involved in mismatch repair, possibly due to their proximity to tumor suppressor genes involved in tumor progression of embryonal form of childhood rhabdomyosarcoma, could explain the observed phenomenon.
复制错误（RERs）最初是在遗传性非息肉病性结肠癌和林奇综合征II的其他肿瘤中发现的。参与错配修复的基因突变会导致突变表型，从而产生RERs。突变表型被认为易引发恶性转化。在此我们表明，在儿童横纹肌肉瘤的胚胎型中也会出现RERs，但与遗传性非息肉病性结肠癌不同的是，所分析的微卫星位点中只有一部分显示出RERs。RERs的出现与等位基因缺失分数增加密切相关（P < 0.001），这表明RERs的出现是横纹肌肉瘤中的一种继发现象。参与错配修复的基因可能因与儿童横纹肌肉瘤胚胎型肿瘤进展中涉及的肿瘤抑制基因相邻而巧合性缺失，这可以解释所观察到的现象。
