Chagtai Tasnim, Zill Christina, Dainese Linda, Wegert Jenny, Savola Suvi, Popov Sergey, Mifsud William, Vujanić Gordan, Sebire Neil, Le Bouc Yves, Ambros Peter F, Kager Leo, O'Sullivan Maureen J, Blaise Annick, Bergeron Christophe, Mengelbier Linda Holmquist, Gisselsson David, Kool Marcel, Tytgat Godelieve A M, van den Heuvel-Eibrink Marry M, Graf Norbert, van Tinteren Harm, Coulomb Aurore, Gessler Manfred, Williams Richard Dafydd, Pritchard-Jones Kathy
Tasnim Chagtai, William Mifsud, Neil Sebire, Richard Dafydd Williams, and Kathy Pritchard-Jones, University College London Institute of Child Health, London; Sergey Popov, University Hospital of Wales; Gordan Vujanić, Cardiff University School of Medicine, Cardiff, United Kingdom; Christina Zill, Jenny Wegert, and Manfred Gessler, Wuerzburg University, Wuerzburg; Marcel Kool, German Cancer Research Center, Heidelberg; Norbert Graf, Saarland University Hospital, Homburg, Germany; Linda Dainese, Yves Le Bouc, Annick Blaise, and Aurore Coulomb, Sorbonne Universités; Linda Dainese, Yves Le Bouc, and Aurore Coulomb, Assistance Publique Hôpitaux de Paris-Hôpital Armand Trousseau, Paris; Christophe Bergeron, Centre Léon Bérard, Lyon, France; Suvi Savola, MRC-Holland; Harm van Tinteren, Netherlands Cancer Institute, Amsterdam; Godelieve A.M. Tytgat and Marry M. van den Heuvel-Eibrink, Princess Maxima Center for Pediatric Oncology/Hematology, Utrecht, the Netherlands; Peter F. Ambros and Leo Kager, Children's Cancer Research Institute; Leo Kager, St Anna Children's Hospital, Vienna, Austria; Maureen J. O'Sullivan, Our Lady's Children's Hospital, Dublin, Ireland; and Linda Holmquist Mengelbier and David Gisselsson, Lund University, Lund, Sweden.
J Clin Oncol. 2016 Sep 10;34(26):3195-203. doi: 10.1200/JCO.2015.66.0001. Epub 2016 Jul 18.
Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series.
WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest.
One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P < .001; hazard ratio, 2.33) and OS (P = .01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss.
Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.
肾母细胞瘤（WT）是最常见的小儿肾肿瘤。国际小儿肿瘤学会（SIOP）方案下的治疗规划基于分期以及对术前化疗反应的组织学评估。尽管总体生存率（OS）较高，但许多无特定危险因素的患者会复发，且许多成功接受治疗的患者会面临具有显著远期效应风险的治疗。为了研究分子生物标志物是否能改善风险分层，我们在一个大型WT系列中评估了1q状态和其他潜在的拷贝数生物标志物。
使用多重连接依赖探针扩增（MLPA）分析对来自586例SIOP WT 2001患者的WT肾切除样本进行分析，该分析可测量1q和其他感兴趣区域的拷贝数。
586例WT中有167例（28%）存在1q增益。1q增益患者的5年无事件生存率（EFS）为75.0%（95%CI，68.5%至82.0%），无增益患者为88.2%（95%CI，85.0%至91.4%）。有增益患者的OS为88.4%（95%CI，83.5%至93.6%），无增益患者为94.4%（95%CI，92.1%至96.7%）。在单变量分析中，1q增益与较差的EFS（P <.001；风险比，2.33）和OS（P =.01；风险比，2.16）相关。在针对1p和16q缺失、性别、分期、年龄和组织学风险组进行调整的多变量分析中，1q增益与较差EFS的关联仍具有显著性。在仅限于中危局限性疾病或非间变局限性疾病的肿瘤亚组中，1q增益仍与较差的EFS相关。与较差EFS相关的其他显著异常包括MYCN增益和TP53缺失。
除术前化疗的组织学反应和肿瘤分期外，1q增益是WT中一种潜在有价值的预后生物标志物。
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