Oncotarget

Research Papers:

Concurrent somatic mutations in driver genes were significantly correlated with lymph node metastasis and pathological types in solid tumors

Yanan Cheng, Shaojing Wang, Lei Han, Pengpeng Liu, Hui Li, Xiubao Ren, Jinpu Yu _ and Xishan Hao

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Oncotarget. 2017; 8:68746-68757. https://doi.org/10.18632/oncotarget.19975

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Abstract

Yanan Cheng1,2,*, Shaojing Wang3,*, Lei Han1,2, Pengpeng Liu1,2, Hui Li4,5, Xiubao Ren6,7, Jinpu Yu1,2 and Xishan Hao1,2,6,7

1Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China

2Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China

3Tianjin Novcare Biotech., Ltd., Tianjin 300300, China

4Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China

5Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China

6Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China

7Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China

*These authors have contributed equally to this work

Correspondence to:

Jinpu Yu, email: yujinpu@tjmuch.com

Keywords: NGS, tumor genetic profiling, concurrent somatic mutations, solid tumors, NSCLC

Received: December 28, 2016    Accepted: July 18, 2017    Published: August 07, 2017

ABSTRACT

To demonstrate the mutational profiles in solid tumors, we profiled 165 solid tumor samples, including 9 cancer types and 4 sample types, by using amplicon-based next-generation sequencing panel covering 48 highly mutated tumorigenesis-related genes that were deep sequenced at an average coverage of 2000×. Both tumor and sample types had significant effect on tumor genetic mutational profiles. Concurrent driver mutations were frequently detected in solid tumor, concentrating on both modes of action driver genes (activating or loss of function). Furthermore, in non-small cell lung cancer (NSCLC), concurrent driver mutations were also significantly correlated with the lymph node metastasis status and pathological types. Higher frequency of lymph node metastasis was observed in patients with NSCLC with concurrent mutations on at least two driver genes. In addition, patients with lung adenocarcinoma were more likely to harbor concurrent driver mutations than patients with lung squamous and large cell carcinoma. Multiple mutations in the epidermal growth factor receptor gene were more frequently detected in patients with refractory NSCLC compared to untreated naive ones. Therefore, concurrent multiple driver mutations, rather than a single genetic mutation, should be investigated extensively to probe novel genetic biomarkers with clinical benefits.


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