Kondelin Johanna, Tuupanen Sari, Gylfe Alexandra E, Aavikko Mervi, Renkonen-Sinisalo Laura, Järvinen Heikki, Böhm Jan, Mecklin Jukka-Pekka, Andersen Claus L, Vahteristo Pia, Pitkänen Esa, Aaltonen Lauri A
Medicum/Department of Medical and Clinical Genetics, University of Helsinki, 00014, Helsinki, Finland,
Fam Cancer. 2015 Sep;14(3):449-53. doi: 10.1007/s10689-015-9804-1.
Approximately 15% of colorectal cancers exhibit instability of short nucleotide repeat regions, microsatellites. These tumors display a unique clinicopathologic profile and the microsatellite instability status is increasingly used to guide clinical management as it is known to predict better prognosis as well as resistance to certain chemotherapeutics. A panel of five repeats determined by the National Cancer Institute, the Bethesda panel, is currently the standard for determining the microsatellite instability status in colorectal cancer. Recently, a quasimonomorphic mononucleotide repeat 16T/U at the 3' untranslated region of the Ewing sarcoma breakpoint region 1 gene was reported to show perfect sensitivity and specificity in detecting mismatch repair deficient colorectal, endometrial, and gastric cancers in two independent populations. To confirm this finding, we replicated the analysis in 213 microsatellite unstable colorectal cancers from two independent populations, 148 microsatellite stable colorectal cancers, and the respective normal samples by PCR and fragment analysis. The repeat showed nearly perfect sensitivity for microsatellite unstable colorectal cancer as it was altered in 212 of the 213 microsatellite unstable (99.5%) and none of the microsatellite stable colorectal tumors. This repeat thus represents the first potential single marker for detecting microsatellite instability.
大约15%的结直肠癌表现出短核苷酸重复序列（微卫星）的不稳定性。这些肿瘤具有独特的临床病理特征，微卫星不稳定性状态越来越多地用于指导临床管理，因为已知它能预测更好的预后以及对某些化疗药物的耐药性。由美国国立癌症研究所确定的包含五个重复序列的一组（贝塞斯达组）目前是确定结直肠癌微卫星不稳定性状态的标准。最近，据报道，尤文肉瘤断点区域1基因3'非翻译区的一个准单态单核苷酸重复序列16T/U在两个独立人群中检测错配修复缺陷型结直肠癌、子宫内膜癌和胃癌时显示出完美的敏感性和特异性。为了证实这一发现，我们通过聚合酶链反应（PCR）和片段分析，在来自两个独立人群的213例微卫星不稳定型结直肠癌、148例微卫星稳定型结直肠癌以及各自的正常样本中重复了该分析。该重复序列对微卫星不稳定型结直肠癌显示出近乎完美的敏感性，因为在213例微卫星不稳定型结直肠癌中有212例（99.5%）发生了改变，而微卫星稳定型结直肠肿瘤中无一例发生改变。因此，这个重复序列代表了检测微卫星不稳定性的首个潜在单一标志物。
