Integration of Recurrent Somatic Mutations with Clinical Outcomes: A Pooled Analysis of 1049 Patients with Clear Cell Renal Cell Carcinoma.
Integration of Recurrent Somatic Mutations with Clinical Outcomes: A Pooled Analysis of 1049 Patients with Clear Cell Renal Cell Carcinoma.
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DOI：
10.1016/j.euf.2016.06.015
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发表时间：
2017-10
影响因子：
5.4
通讯作者：
Hakimi AA
中科院分区：
文献类型：
--
作者：
Manley BJ;Zabor EC;Casuscelli J;Tennenbaum DM;Redzematovic A;Becerra MF;Benfante N;Sato Y;Morikawa T;Kume H;Fukayama M;Homma Y;Ogawa S;Arcila ME;Voss MH;Feldman DR;Coleman JA;Reuter VE;Motzer RJ;Russo P;Hsieh JJ;Hakimi AA
肾透明细胞癌(CcRCC)的临床病理结果与复发的体细胞突变之间的相关性分析仅限于个体队列。目的：明确特定突变与ccRCC疾病特征之间的临床病理联系。DNA测序数据来自三个合作基因组队列(n=754)和我们的机构数据库(n=295)。所有患者均有临床资料和原发肿瘤体细胞突变的鉴定。分析基因突变与最大肿瘤大小(线性回归)和病理分期(Logistic回归)的关系。采用竞争风险法计算肿瘤特异性生存率(CS)和无复发生存率(RFS)。分析针对队列位置进行调整，结果针对多次测试(Q值)进行调整。相关基因用于多变量模型，包括混杂变量和经过验证的Mayo临床分期、大小、分级和坏死(SSIGN)评分。BAP1基因突变与肿瘤大小相关(q=0.013)。经校正分析，未发现突变与分期相关。在多变量模型中，BAP1(q=0.004)和TP53(q=0.001)的突变与CS降低相关；当包括SSIGN评分时，只有TP53(q=0.005)仍然显著。在多变量模型中，包括SSIGN评分的模型中，SETD2突变(q=0.047)与RFS降低相关。在1000名慢性肾细胞癌患者中，合并分析和多变量模型显示，三个突变基因与不良的临床结果有统计学意义的相关性。这包括较常见的突变BAP1和SETD2以及较少突变的TP53。在调整了临床混杂因素后，TP53和SETD2基因突变分别与CS和RFS降低相关。使用严格的统计学方法，这项研究证实，肾透明细胞癌的某些突变可能预示着较差的存活率和较高的复发风险。
Analyses of associations between clinicopathologic outcomes and recurrent somatic mutations in clear cell renal cell carcinoma (ccRCC) have been limited to individual cohorts. To define clinicopathologic associations between specific mutations and ccRCC disease characteristics. DNA sequencing data were pooled from three collaborative genomic cohorts (n = 754) and our institutional database (n = 295). All patients had clinical data and identification of somatic mutations from their primary tumors. Analysis of gene mutations for associations with maximal tumor size (linear regression) and pathologic stage (logistic regression). Cancer-specific survival (CSS) and recurrence-free survival (RFS) were calculated using competing risks methods. Analyses were adjusted for cohort site, and results were adjusted for multiple testing (q value). Relevant genes were used in multivariable models that included confounding variables and the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score. Association with tumor size was found for mutations in BAP1 (q = 0.013). No mutations were found to be associated with stage after adjusted analysis. Mutations in BAP1 (q = 0.004) and TP53 (q = 0.001) were associated with decreased CSS in a multivariable model; only TP53 (q = 0.005) remained significant when SSIGN score was included. SETD2 mutations (q = 0.047) were associated with decreased RFS in multivariable models, including models with SSIGN score. In >1000 patients with ccRCC, pooled analysis and multivariable modeling demonstrated that three mutated genes have statistically significant associations with poor clinical outcomes. This included the more commonly mutated BAP1 and SETD2 and the less frequently mutated TP53. After adjustment for clinical confounders, mutations of TP53 and SETD2 were associated with decreased CSS and RFS, respectively. Using rigorous statistical methods, this study affirmed that certain mutations in clear cell renal cell carcinomamay portend inferior survival and an increased risk of recurrence.
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通过BAP1和PBRM1表达鉴定的透明细胞肾细胞癌亚型。
DOI：
10.1016/j.juro.2015.07.113
发表时间：
2016-01
期刊：
The Journal of urology
影响因子：
--
作者：
Joseph RW;Kapur P;Serie DJ;Parasramka M;Ho TH;Cheville JC;Frenkel E;Parker AS;Brugarolas J
通讯作者：
Brugarolas J
BRCA1相关蛋白-1是一种需要去泛素化活性和核定位的肿瘤抑制剂。
影响因子：
11.2
作者：
Ventii KH;Devi NS;Friedrich KL;Chernova TA;Tighiouart M;Van Meir EG;Wilkinson KD
通讯作者：
Wilkinson KD
DOI：
10.1158/1078-0432.ccr-12-3886
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hakimi AA;Ostrovnaya I;Reva B;Schultz N;Chen YB;Gonen M;Liu H;Takeda S;Voss MH;Tickoo SK;Reuter VE;Russo P;Cheng EH;Sander C;Motzer RJ;Hsieh JJ;ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
通讯作者：
ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
影响因子：
6.6
作者：
Hakimi, A. Ari;Mano, Roy;Ciriello, Giovanni;Gonen, Mithat;Mikkilineni, Nina;Sfakianos, John P.;Kim, Philip H.;Motzer, Robert J.;Russo, Paul;Reuter, Victor E.;Hsieh, James J.;Ostrovnaya, Irina
通讯作者：
Ostrovnaya, Irina
影响因子：
30.8
作者：
Pena-LlopiS, Samuel;Vega-Rubin-de-Celis, Silvia;Liao, Arnold;Leng, Nan;Pavia-Jimenez, Andrea;Wang, Shanshan;Yamasaki, Toshinari;Zhrebker, Leah;Sivanand, Sharanya;Spence, Patrick;Kinch, Lisa;Hambuch, Tina;Jain, Suneer;Lotan, Yair;Margulis, Vitaly;Sagalowsky, Arthur I.;Summerour, Pia Banerji;Kabbani, Wareef;Wong, S. W. Wendy;Grishin, Nick;Laurent, Marc;Xie, Xian-Jin;Haudenschild, Christian D.;Ross, Mark T.;Bentley, David R.;Kapur, Payal;Brugarolas, James
通讯作者：
Brugarolas, James