Oncotarget

Research Papers:

Comprehensive analysis of targetable oncogenic mutations in chinese cervical cancers

Libing Xiang, Jiajia Li, Wei Jiang, Xuxia Shen, Wentao Yang, Xiaohua Wu and Huijuan Yang _

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Oncotarget. 2015; 6:4968-4975. https://doi.org/10.18632/oncotarget.3212

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Abstract

Libing Xiang1, Jiajia Li1, Wei Jiang1, Xuxia Shen2, Wentao Yang2, Xiaohua Wu1 and Huijuan Yang1

1 Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

2 Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence:

Huijuan Yang, email:

Keywords: Oncogenic mutation, Cervical cancers, PI3K pathway genes, RTK genes, RAS genes

Received: November 01, 2014 Accepted: December 27, 2014 Published: December 31, 2014

Abstract

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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