Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.
Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.
复制标题
DOI：
10.1111/cas.12601
复制
发表时间：
2015-03
期刊：
影响因子：
5.7
通讯作者：
Nakatani Y
中科院分区：
文献类型：
--
作者：
Furuya M;Hong SB;Tanaka R;Kuroda N;Nagashima Y;Nagahama K;Suyama T;Yao M;Nakatani Y
Birt-Hogg-Dubé综合征(BHD)是一种与卵泡蛋白基因(Flcn)胚系突变相关的遗传性疾病。受影响的家庭患多发性肾细胞癌(RCC)的风险很高。区分FLCN相关性肾细胞癌和散发性肾细胞癌的诊断标记物尚未被研究，许多未确诊的BHD患者没有得到适当的医疗护理。我们对18例经基因检测确诊的BHD患者的27例肾细胞癌进行了组织病理学研究。通过DNA测序分析肾癌皮损可能的体细胞突变。采用Western blotting和免疫组织化学方法比较FLCN相关肾癌和散发性肾肿瘤(n=62)中FLCN和糖蛋白非转移性B(GPNMB)的表达水平。用定量RT-PCR方法检测GPNMB的表达。组织病理学分析显示，最常见的组织学类型是嫌色肾癌(n=12)，其次是嗜酸性/嫌色混合型肿瘤(n=9.6)。体细胞突变分析显示6例有微小的基因内突变，2例有杂合性丢失。免疫印迹和免疫染色分析显示，与FLCN相关的RCC表现为GPNMB高表达和FLCN低表达，而散发性肿瘤表现为倒置模式。在与FLCN相关的肾癌中，GPNMB mRNA的丰度是散发性肿瘤的23倍。GPNMB和FLCN的独特表达模式可能会识别肾细胞癌患者，这些患者需要进一步研究BHD。
Birt–Hogg–Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.
登录
查看更多内容
影响因子：
3.6
作者：
Tomihari M;Hwang SH;Chung JS;Cruz PD Jr;Ariizumi K
通讯作者：
Ariizumi K
影响因子：
4.5
作者：
Delongchamps, Nicolas B.;Galmiche, Louise;Mejean, Arnaud
通讯作者：
Mejean, Arnaud
影响因子：
3.3
作者：
Chaux, Alcides;Schultz, Luciana;Netto, George J.
通讯作者：
Netto, George J.
影响因子：
2.2
作者：
Menko, Fred H.;Johannesma, Paul C.;Gille, Johan J. P.
通讯作者：
Gille, Johan J. P.
影响因子：
8.8
作者：
通讯作者：
--