Comprehensive analysis of targetable oncogenic mutations in chinese cervical cancers.
Comprehensive analysis of targetable oncogenic mutations in chinese cervical cancers.
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DOI：
10.18632/oncotarget.3212
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Xiang L;Li J;Jiang W;Shen X;Yang W;Wu X;Yang H
应用逆转录聚合酶链反应（RT-PCR）和直接测序法检测了285例中国人宫颈癌组织中16个靶基因的突变。评估其临床病理学相关性和预后意义。在29.8%的癌症中发现了92个非同义体细胞突变。突变率如下：PIK 3CA（12.3%）、KRAS（5.3%）、HER 2（4.2%）、FGFR 3-TACC 3融合（3.9%）、PTEN（2.8%）、FGFR 2（1.8%）、FGFR 3（0.7%）、NRAS（0.7%）、HRAS（0.4%）和EGFR（0.4%）。在AKT 1或BRAF中未检测到突变，并且在任何癌症中均未发现融合FGFR 1-TACC 1、EML 4-ALK、CCDC 6-RET和KIF 5 B-RET。RTK和RAS突变在非鳞状细胞癌中比在鳞状细胞癌中更常见（分别为P=0.043和P=0.042）。RAS突变在年轻患者（<45岁）中更常见（13.7% vs. 7.7%，P=0.027）。RTK突变倾向于在年轻患者中更常见，而PIK 3CA/PTEN/AKT突变倾向于在老年患者中更常见。RAS突变与疾病复发显著相关。据我们所知，这是第一次在一个大型宫颈癌病例队列中对主要靶向致癌基因突变进行全面分析。我们的数据显示，相当一部分宫颈癌患者携带已知的药物突变，并可能从靶向治疗中获益。
Mutations in 16 targetable oncogenic genes were examined using reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing in 285 Chinese cervical cancers. Their clinicopathological relevance and prognostic significance was assessed. Ninety-two nonsynonymous somatic mutations were identified in 29.8% of the cancers. The mutation rates were as follows: PIK3CA (12.3%), KRAS (5.3%), HER2 (4.2%), FGFR3-TACC3 fusions (3.9%), PTEN (2.8%), FGFR2 (1.8%), FGFR3 (0.7%), NRAS (0.7%), HRAS (0.4%) and EGFR (0.4%). No mutations were detected in AKT1 or BRAF, and the fusions FGFR1-TACC1, EML4-ALK, CCDC6-RET and KIF5B-RET were not found in any of the cancers. RTK and RAS mutations were more common in non-squamous carcinomas than in squamous carcinomas (P=0.043 and P=0.042, respectively). RAS mutations were more common in young patients (<45 years) (13.7% vs. 7.7%, P=0.027). RTK mutations tended to be more common in young patients, whereas PIK3CA/PTEN/AKT mutations tended to be more common in old patients. RAS mutations were significantly associated with disease relapse. To our knowledge, this is the first comprehensive analysis of major targetable oncogenic mutations in a large cohort of cervical cancer cases. Our data reveal that a considerable proportion of patients with cervical cancers harbor known druggable mutations and might benefit from targeted therapy.
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影响因子：
6.2
作者：
Wright, Alexi A.;Howitt, Brooke E.;Myers, Andrea P.;Dahlberg, Suzanne E.;Palescandolo, Emanuele;Van Hummelen, Paul;MacConaill, Laura E.;Shoni, Melina;Wagle, Nikhil;Jones, Robert T.;Quick, Charles M.;Laury, Anna;Katz, Ingrid T.;Hahn, William C.;Matulonis, Ursula A.;Hirsch, Michelle S.
通讯作者：
Hirsch, Michelle S.
DOI：
10.1056/nejmoa1007056
发表时间：
2010-10-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Butrynski JE;D'Adamo DR;Hornick JL;Dal Cin P;Antonescu CR;Jhanwar SC;Ladanyi M;Capelletti M;Rodig SJ;Ramaiya N;Kwak EL;Clark JW;Wilner KD;Christensen JG;Jänne PA;Maki RG;Demetri GD;Shapiro GI
通讯作者：
Shapiro GI
影响因子：
28.2
作者：
Drilon A;Wang L;Hasanovic A;Suehara Y;Lipson D;Stephens P;Ross J;Miller V;Ginsberg M;Zakowski MF;Kris MG;Ladanyi M;Rizvi N
通讯作者：
Rizvi N
影响因子：
11.2
作者：
Janku F;Wheler JJ;Naing A;Falchook GS;Hong DS;Stepanek VM;Fu S;Piha-Paul SA;Lee JJ;Luthra R;Tsimberidou AM;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
5.1
作者：
Chen, Wanqing;Zheng, Rongshou;He, Jie
通讯作者：
He, Jie