Abstract
BackgroundDeregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development. Although mutations in the downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers, extensive mutation and copy number analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC).MethodsWe examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients.We used DNA sequencing to detect mutations and the copy number changes were evaluated by qPCR and array comparative genomic hybridization (CGH) analysis.ResultsWe examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We identified 3 mutations (2.6%) in K-RAS and 3 mutations (2.6%) in PIK3CA. Copy number amplification was found in 37 cases (32.2%) for PIK3CA, 10 cases (8.7%) for K-RAS and 2 cases (1.7%) for BRAF. Kaplan-Meier survival analysis revealed that copy-number amplification of PIK3CA was markedly associated with cancer relapse in patients without lymph node metastasis. (Log-rank test, p = 0.026)ConclusionsCopy number amplification of the PIK3CA gene is associated with poor prognosis in HNSCC patients without lymph node metastasis. The PIK3CA copy number status will serve as a marker of poor prognosis in patients with HNSCC.
Highlights
Deregulation of the epidermal growth factor receptor (EGFR) signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development
Mutation analysis of KRAS, BRAF and PIK3CA We conducted a sequencing analysis to examine the frequency of mutations in the KRAS, BRAF and PIK3CA genes, and we investigated the correlations between the presence of mutations and the clinical data
Copy number analysis of KRAS, BRAF and PIK3CA We identified copy number changes in PIK3CA, K-RAS and BRAF
Summary
Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development. Mutations in the downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers, extensive mutation and copy number analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC). In many types of malignancies, such as lung cancer and colorectal cancer, mutations in the genes encoding EGFR or downstream components of the signaling pathways are highly prevalent [5,6]. These mutations are often associated with the effectiveness of molecularly targeted drugs. We determined a type of the mutation to investigate in reference to some theses about HNSCC in KRAS, BRAF, and PIK3CA [9,10]
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