Copy Number Amplification of the PIK3CA Gene Is Associated with Poor Prognosis in Non-lymph node metastatic Head and Neck Squamous Cell Carcinoma
Open Access
- 20 September 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 12 (1), 416
- https://doi.org/10.1186/1471-2407-12-416
Abstract
Background: Deregulation 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). Methods: We 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. Results: We 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) Conclusions: Copy 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.Keywords
This publication has 41 references indexed in Scilit:
- Faculty Opinions recommendation of High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.Published by H1 Connect ,2013
- Gene status of head and neck squamous cell carcinoma cell lines and cetuximab‐mediated biological activitiesCancer Science, 2011
- PIK3CA Mutations in Patients with Advanced Cancers Treated with PI3K/AKT/mTOR Axis InhibitorsMolecular Cancer Therapeutics, 2011
- High Frequency of Mutations of the PIK3CA Gene in Human CancersScience, 2004
- Epidermal Growth Factor Receptor in Non–Small-Cell Lung Carcinomas: Correlation Between Gene Copy Number and Protein Expression and Impact on PrognosisJournal of Clinical Oncology, 2003
- BRAF mutations in metastatic melanoma: a possible association with clinical outcome.2003
- BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma.2003
- New TNM staging criteria for head and neck tumorsSeminars in Surgical Oncology, 2003
- Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia.2002
- Alcohol, smoking, and occupational factors in cancer of the larynx: A case-control studyAmerican Journal of Industrial Medicine, 1991