Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix.
Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix.
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DOI：
10.1002/cncr.28288
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发表时间：
2013-11-01
期刊：
影响因子：
6.2
通讯作者：
Hirsch, Michelle S.
中科院分区：
文献类型：
--
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.
关键词：
宫颈癌是全世界妇女癌症死亡的第二大原因。我们试图描述宫颈癌中最常见的致癌突变，并探索两种最常见的组织学亚型：腺癌和鳞状细胞癌之间的基因组差异。一种名为Oncomap的高通量基因分型平台被用于查询80个宫颈肿瘤中139个癌基因中的1250个已知突变。样品使用基于质谱的基因分型平台（Sequenom）进行分析，并使用正交化学进行验证。通过大规模平行测序（Illumina）进一步验证EGFR突变。同时进行人乳头瘤病毒（HPV）基因分型。60.0%（48/80）的肿瘤检测到验证突变。突变率最高的是PIK3CA（31.3%）、KRAS（8.8%）和EGFR（3.8%）。PIK3CA突变率在腺癌和鳞状细胞癌中无显著差异（分别为25.0%和37.5%,p=0.33）。相比之下，KRAS突变仅在腺癌中被发现（17.5%对0%，p=0.01），一种新的EGFR突变仅在鳞状细胞癌中被发现（0%对7.5%,p=0.24）。HPV-16或HPV-18与体细胞突变或总体生存之间没有关联。在校正分析中，PIK3CA突变与较短的生存期相关，分别为67.1个月和90.3个月（HR=9.1, 95% CI 2.8-29.5, p<0.001）。子宫颈癌具有很高的潜在靶向性致癌突变率。此外，宫颈鳞状细胞癌和腺癌具有不同的分子特征，这表明使用更有针对性的治疗策略，包括pi3激酶和MEK抑制剂，可能会改善临床结果。
Cervical cancer is the second leading cause of cancer deaths among women worldwide. We sought to describe the most common oncogenic mutations in cervical cancers, and to explore genomic differences between the two most common histological subtypes: adenocarcinoma and squamous cell carcinoma. A high-throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry-based genotyping platform (Sequenom), and validated with an orthogonal chemistry. EGFR mutations were further validated by massively parallel sequencing (Illumina). Human papilloma virus (HPV) genotyping was also performed. Validated mutations were detected in 60.0% (48/80) of tumors examined. The highest mutation rates were PIK3CA (31.3%), KRAS (8.8%), and EGFR (3.8%). PIK3CA mutation rates were not significantly different in adenocarcinoma and squamous cell carcinomas (25.0% vs. 37.5%, respectively, p=0.33). In contrast, KRAS mutations were identified only in adenocarcinoma (17.5% vs. 0%, p=0.01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs. 7.5%, p=0.24). There were no associations between HPV-16 or HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival—67.1 vs. 90.3 months (HR=9.1, 95% CI 2.8–29.5, p<0.001). Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3-kinase and MEK inhibitors.
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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：
45.3
作者：
Lai, Chyong-Huey;Chang, Chee-Jen;Chang, Ting-Chieh
通讯作者：
Chang, Ting-Chieh
影响因子：
11.5
作者：
Halle, Cathinka;Lando, Malin;Lyng, Heidi
通讯作者：
Lyng, Heidi
影响因子：
8.8
作者：
Iida, K.;Nakayama, K.;Rahman, M. T.;Rahman, M.;Ishikawa, M.;Katagiri, A.;Yeasmin, S.;Otsuki, Y.;Kobayashi, H.;Nakayama, S.;Miyazaki, K.
通讯作者：
Miyazaki, K.
影响因子：
4.7
作者：
EIFEL, PJ;BURKE, TW;SMITH, TL
通讯作者：
SMITH, TL