Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors.
Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors.
复制标题
干细胞因子受体 (c-KIT) 密码子 816 突变可预测双侧睾丸生殖细胞肿瘤的发展。
作者：
L. Looijenga;H. de Leeuw;Monique van Oorschot;R. van Gurp;H. Stoop;A. Gillis;C. A. de Gouveia Brazao;R. Weber;W. Kirkels;T. V. van Dijk;M. von Lindern;P. Valk;Geczy Lajos;E. Oláh;J. Nesland;S. Fosså;J. Oosterhuis
青少年和成人的睾丸生殖细胞肿瘤（TGCT）起源于管内生殖细胞肿瘤（ITGCN），它由胚胎生殖细胞的恶性对应物组成。 ITGCN 细胞的特征之一是存在干细胞因子受体 c-KIT。 ITGCN一旦成立，将始终向侵入性方向发展。大约 2.5-5% 的 TGCT 患者会出现双侧疾病并需要完全去势，从而导致不孕、需要终生补充雄激素以及心理压力。迄今为止，预测对侧肿瘤的唯一方法是对侧睾丸进行手术活检以证明 ITGCN。我们对 224 例单侧 TGCT 和 61 例经证实的双边 TGCT（来自欧洲三个独立收集的系列中的 46 名患者）进行了回顾性研究，以确定激活 c-KIT 密码子 816 突变的存在。在 3 个单侧 TGCT（1.3%）和 57 个双侧 TGCT（93%；P < 0.0001）中发现了 c-KIT 密码子 816 突变。在 ITGCN 可用的两个野生型双侧肿瘤中，侵袭前细胞含有突变。这些突变起源于体细胞，并且在两种肿瘤中都是相同的。我们得出结论，体细胞激活密码子 816 c-KIT 突变与双侧 TGCT 的发生有关。在单侧 TGCT 中检测 c-KIT 密码子 816 突变可识别有双侧疾病风险的患者。这些患者可能会接受量身定制的治疗，以防止双侧疾病的发展，同时保留睾丸激素功能。
Testicular germ-cell tumors (TGCTs) of adolescents and adults originate from intratubular germ cell neoplasia (ITGCN), which is composed of the malignant counterparts of embryonal germ cells. ITGCN cells are characterized, among others, by the presence of stem cell factor receptor c-KIT. Once established, ITGCN will always progress to invasiveness. Approximately 2.5-5% of patients with a TGCT will develop bilateral disease and require complete castration, resulting in infertility, a need for lifelong androgen replacement, and psychological stress. To date, the only way to predict a contralateral tumor is surgical biopsy of the contralateral testis to demonstrate ITGCN. We did a retrospective study of 224 unilateral and 61 proven bilateral TGCTs (from 46 patients, in three independently collected series in Europe) for the presence of activating c-KIT codon 816 mutations. A c-KIT codon 816 mutation was found in three unilateral TGCT (1.3%), and in 57 bilateral TGCTs (93%; P < 0.0001). In the two wild-type bilateral tumors for which ITGCN was available, the preinvasive cells contained the mutation. The mutations were somatic in origin and identical in both tumors. We conclude that somatic activating codon 816 c-KIT mutations are associated with development of bilateral TGCT. Detection of c-KIT codon 816 mutations in unilateral TGCT identifies patients at risk for bilateral disease. These patients may undergo tailored treatment to prevent the development of bilateral disease, with retention of testicular hormonal function.
影响因子：
6
作者：
Tian, QS;Frierson, HF;Moskaluk, CA
通讯作者：
Moskaluk, CA