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与上尿路尿路上皮癌淋巴管侵犯相关的DNA拷贝数畸变

DNA copy number aberrations associated with lymphovascular invasion in upper urinary tract urothelial carcinoma.

作者信息

Misumi Taku, Yamamoto Yoshiaki, Miyachika Yoshihiro, Eguchi Satoshi, Chochi Yasuyo, Nakao Motonao, Nagao Kazuhiro, Hara Takahiko, Sakano Shigeru, Furuya Tomoko, Oga Atsunori, Kawauchi Shigeto, Sasaki Kohsuke, Matsuyama Hideyasu

机构信息

Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.

出版信息

Cancer Genet. 2012 Jun;205(6):313-8. doi: 10.1016/j.cancergen.2012.04.008.

Abstract

Recent studies have reported that lymphovascular invasion (LVI) is a predictor of patient prognosis in upper urinary tract urothelial carcinoma (UUTUC). DNA copy number aberrations (DCNAs) identified by array-based comparative genomic hybridization (aCGH) had not previously been examined in UUTUC. We therefore examined DCNAs in UUTUC and compared them with DCNAs in LVI. We applied aCGH technology using DNA chips spotted with 4,030 BAC clones to 32 UUTUC patients. Frequent copy number gains were detected on chromosomal regions 8p23.1 and 20q13.12, whereas frequent copy number losses were detected on chromosomal regions 13q21.1, 17p13.1, 6q16.3, and 17p11.2. DCNAs occurred more frequently in tumors with LVI than in those without it (P = 0.0002), and this parameter was more closely associated with LVI than with the tumor grade or pT stage. Disease-specific survival rate was higher in tumors without LVI than in those with it (P = 0.0120); however, tumor grade and stage were not significant prognostic factors of patient outcome. These data support our hypothesis that tumors with LVI have more genetic alterations in terms of total numbers of DCNAs than those without, and provide proof that aggressive adjuvant therapy should be considered for UUTUC patients with LVI.

摘要

近期研究报道,淋巴管浸润(LVI)是上尿路尿路上皮癌(UUTUC)患者预后的一个预测指标。此前尚未对基于阵列比较基因组杂交(aCGH)鉴定出的DNA拷贝数畸变(DCNAs)在上尿路尿路上皮癌中的情况进行研究。因此,我们对上尿路尿路上皮癌中的DCNAs进行了检测,并将其与有淋巴管浸润的DCNAs进行比较。我们使用点有4030个BAC克隆的DNA芯片的aCGH技术对32例上尿路尿路上皮癌患者进行检测。在染色体区域8p23.1和20q13.12检测到频繁的拷贝数增加,而在染色体区域13q21.1、17p13.1、6q16.3和17p11.2检测到频繁的拷贝数减少。有淋巴管浸润的肿瘤中DCNAs的发生频率高于无淋巴管浸润的肿瘤(P = 0.0002),并且该参数与淋巴管浸润的相关性比与肿瘤分级或pT分期的相关性更强。无淋巴管浸润的肿瘤的疾病特异性生存率高于有淋巴管浸润的肿瘤(P = 0.0120);然而,肿瘤分级和分期不是患者预后的显著预后因素。这些数据支持了我们的假设,即有淋巴管浸润的肿瘤在DNA拷贝数畸变总数方面比无淋巴管浸润的肿瘤有更多的基因改变,并证明对于有淋巴管浸润的上尿路尿路上皮癌患者应考虑积极的辅助治疗。

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