Limpaiboon Temduang, Tapdara Sumonta, Jearanaikoon Patcharee, Sripa Banchob, Bhudhisawasdi Vajarabhongsa
Department of Clinical Chemistry, Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
World J Gastroenterol. 2006 Jul 21;12(27):4377-82. doi: 10.3748/wjg.v12.i27.4377.
To investigate loss of heterozygosity (LOH) and microsatellite instability (MSI) on the chromosomal region 1p36-pter in cholangiocarcinoma (CCA) patients and determine the association between microsatellite alterations and clinicopathological parameters.
Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer.
Sixty-eight out of 90 cases (75.6%) showed LOH in one or more loci. LOH was found most frequently at D1S199 (40.0%), D1S507 (34.6%), D1S2845 (30.5%), and D1S2734 (30.1%). MSI was found in 34 of 90 cases (37.8%) at one or more loci. Fine mapping at 1p36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion (P = 0.017), whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without (P = 0.031). LOH at D1S2845 showed a significant correlation with nerve invasion (P = 0.029). Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis (P = 0.0026).
Allelic loss plays a major role in microsatellite alterations at chromosome 1p36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.
研究胆管癌（CCA）患者染色体区域1p36 - pter的杂合性缺失（LOH）和微卫星不稳定性（MSI），并确定微卫星改变与临床病理参数之间的关联。
使用GS - 3000凝胶扫描片段自动分析仪确定10个多态性微卫星标记用于检测LOH和MSI。
90例患者中有68例（75.6%）在一个或多个位点显示LOH。在D1S199（40.0%）、D1S507（34.6%）、D1S2845（30.5%）和D1S2734（30.1%）位点发现LOH最为常见。90例患者中有34例（37.8%）在一个或多个位点显示MSI。1p36的精细定位显示两个明显的常见缺失区域，即D1S2845以及D1S507和D1S2734之间25.5厘摩的区域，表明存在可能在CCA发生中起重要作用的假定肿瘤抑制基因。D1S234发生LOH的患者淋巴侵犯较少（P = 0.017），而D1S2676发生LOH的患者比未发生者表现出更多的淋巴侵犯（P = 0.031）。D1S2845的LOH与神经侵犯显著相关（P = 0.029）。此外，在D1S228显示MSI的患者预后较差（P = 0.0026）。
等位基因缺失在染色体1p36的微卫星改变中起主要作用，这可能有助于肝吸虫相关CCA的致癌作用和发病机制，并且这些改变可作为CCA患者的分子预后指标。
