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PIK3CA mutations in head and neck squamous cell carcinoma
Wanglong Qiu1, Frank Schönleben, Xiaojun Li
1Department of Otolaryngology/Head and Neck Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Purpose:
Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic alpha (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC.
Experimental Design:
More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens.
Results:
We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A --> G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples.
Conclusions:
These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.
Insights
Mutations in the PIK3CA gene were found in 11% of head and neck squamous cell carcinoma (HNSCC) cases, particularly in pharyngeal cancer. These PIK3CA mutations may drive cancer development, suggesting PIK3CA inhibitors as potential therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in the phosphoinositide-3-kinase catalytic alpha (PIK3CA) gene are frequent in human solid tumors.
- While PIK3CA gene amplifications are known in head and neck squamous cell carcinoma (HNSCC), its small mutations have not been previously assessed.
Purpose of the Study:
- To determine the frequency of PIK3CA gene mutations in HNSCC.
- To investigate the role of PIK3CA in HNSCC tumorigenesis.
Main Methods:
- Direct genomic DNA sequencing was used to analyze key exons (1, 4, 5, 6, 7, 9, and 20) of the PIK3CA gene.
- The study included 38 HNSCC specimens, focusing on regions known to harbor somatic mutations (exons 9 and 20).
Main Results:
- Four missense mutations in PIK3CA were identified in 11% (4 out of 38) of HNSCC specimens.
- Three known hotspot mutations (H1047R, E542K, E545K) and one novel mutation (Y343C) were detected.
- Three mutations were somatic, and three of the four identified mutations were found in pharyngeal cancer samples.
Conclusions:
- The findings suggest that oncogenic PIK3CA mutations contribute to the development of human head and neck cancers, with a notable prevalence in pharyngeal cancer.
- Targeting PIK3CA with specific kinase inhibitors could offer a potential therapeutic strategy for HNSCC, particularly for pharyngeal cancer.
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