Chikwava Kudakwashe R, Hunt Jennifer L, Mantha Geeta S, Murphy Justin E, Jaffe Ronald
University of Pittsburgh School of Medicine and Department of Pathology, Presbyterian University Hospital, PA 15213, USA.
Pediatr Dev Pathol. 2007 Jan-Feb;10(1):18-24. doi: 10.2350/06-02-0045.1.
The contribution of molecular mutations to the progression of Langerhans' cell histiocytosis (LCH) is not well understood. This study analyzes fractional allelic loss (FAL) across a series of tumor suppressor genes (TSGs) comparing LCH of various clinical stages and LCH involving organs of various degrees of prognostic risk. Polymerase chain reaction (PCR) amplification, using fluorescent-labeled primers targeting 6 TSGs, was performed on extracted DNA. The PCR products were analyzed using a capillary electrophoresis genetic analyzer. Ratios of the peak heights in informative cases were compared between unaffected and lesional tissue to identify loss of heterozygosity (LOH). Fisher's exact testing was used to analyze the results. Fourteen children with single-system involvement (SS-LCH) and 10 with multisystem involvement (MS-LCH) were included. High-risk or special-site organ involvement was seen in 13 children and low-risk organ involvement in 10. The mean FAL in MS-LCH (62.7%) was statistically significantly higher than in SS-LCH (40.3%). The FAL in children with risk or special-site LCH (53.2%) was also significantly higher than in children with low-risk LCH (39.6%). Markers on 5q had significantly higher FAL in MS-LCH (76.3%) and children with risk or special-site organ involvement (72.7%) compared with SS-LCH (46.2%) and children with low-risk organ involvement (37.5%). These data suggest that more extensive and higher-risk forms of LCH have evidence of more mutational events at TSGs. Further investigation of the potential use of LOH at 5q23 will be necessary to establish utility for this assay to predict disease progression and poor outcome.
分子突变对朗格汉斯细胞组织细胞增多症（LCH）进展的作用尚未完全明确。本研究分析了一系列肿瘤抑制基因（TSG）中的等位基因缺失分数（FAL），比较了不同临床分期的LCH以及累及不同预后风险器官的LCH。使用针对6个TSG的荧光标记引物对提取的DNA进行聚合酶链反应（PCR）扩增。PCR产物用毛细管电泳基因分析仪进行分析。在信息性病例中，比较未受影响组织和病变组织之间峰高的比率，以确定杂合性缺失（LOH）。采用Fisher精确检验分析结果。纳入了14名单系统受累（SS-LCH）儿童和10名多系统受累（MS-LCH）儿童。13名儿童出现高风险或特殊部位器官受累，10名儿童出现低风险器官受累。MS-LCH的平均FAL（62.7%）在统计学上显著高于SS-LCH（40.3%）。有风险或特殊部位LCH儿童的FAL（53.2%）也显著高于低风险LCH儿童（39.6%）。与SS-LCH（46.2%）和低风险器官受累儿童（37.5%）相比，5q上的标记在MS-LCH（76.3%）以及有风险或特殊部位器官受累儿童（72.7%）中的FAL显著更高。这些数据表明，更广泛和更高风险形式的LCH在TSG处有更多突变事件的证据。有必要进一步研究5q23处LOH的潜在用途，以确定该检测方法在预测疾病进展和不良预后方面的实用性。
