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.
Highlights
Cancer treatment has made paradigm shift advance-ments in the past decade with the development of therapies targeting specific genetic alterations
TruSeq Amplicon Cancer Panel (TSACP) assay is a reliable method to detect multiplex mutations in tumors Profiling of 165 solid tumor tissue samples was performed via amplicon-based target sequencing using Illumina TSACP assay
A total of 8526 variants were identified in 165 solid tumor samples, among which 6174 variants were located in noncoding regions and 1194 variants were synonymous variants
Summary
Cancer treatment has made paradigm shift advance-ments in the past decade with the development of therapies targeting specific genetic alterations. A number of target therapies have shown great antitumor efficiency in the clinic, such as the epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKI) gefitinib and erlotinib for patients with non-small cell lung cancer (NSCLC) harboring sensitizing EGFR www.impactjournals.com/oncotarget mutations [1], crizotinib for patients with NSCLC bearing ALK and ROS1 fusion [1, 2], and Gleevec for patients with gastrointestinal stromal tumor with mutated KIT [3] Tumor genotyping makes it possible to categorize patients into different subgroups and to treat them with the optimal regimens to achieve more satisfactory therapeutic effects. Targeted NGS is efficient and accurate in screening drug targets and provides more treatment options for patients with cancer, especially patients with advanced stage cancer who cannot tolerate the side effects of chemotherapy
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