IADR Abstract Archives
Role of Phosphatidylinositol 3-kinase (PI-3K) in Oral Squamous Cell Carcinoma
Objectives: 1) Determine the relationship between PI-3K mutations and oral squamous cell carcinoma (OSCC) using computational analysis
2) Identify PI-3K mutations in banked OSCC tissues
Methods: In order to determine the relationship between PI-3K mutations and OSCC, computational analysis via public databases was used to select for the OSCC data (n=470;248) among numerous head and neck cancer (HNSC) studies and to explore the DNA level deviations. Additionally, the DNA of formalin-fixed and paraffin-embedded (FFPE) OSCC sections (n=28) in the Penn Medicine tissue bank was isolated to analyze for mutations of components of the PI-3K signaling pathway. The same samples were also tested for immunoreactivity to pAkt (a phosphorylated protein kinase that regulates metabolism and cell survival).
Results: Immunohistochemical methods on the samples showed Akt activation by phosphorylation in OSCC tissues. Data mining methods revealed that approximately one in five OSCC patients possessed somatic point mutations in the genes that encode for enzymes in the PI-3K pathway (e.g. PTEN, a tumor suppressor, and mTOR, a cellular response mediator). The three most frequent single nucleotide mutations for PIK3CA were H1047R, E542K, and E545K. Moreover, a third of the patients had genetic anomalies at copy number alteration (CNA) level, and frequency for loss of heterozygosity (LOH) of PTEN was approximately 40%.
Conclusions: Findings from this study show that members of the PI-3K signaling pathway are promising candidates for personalized OSCC treatments. All findings from this study are consistent with those of previous genomic and immunologic studies of HNSC or OSCC. Although PI-3K pathway activation in a subset of OSCC patients is established, there is not yet a biomarker to clinically identify them beyond extensive genomic profiling.
The LOH rate of 39% in PTEN may be significant, but until more OSCC samples are tested, it will be difficult to onnect the observation to appropriate treatment approaches. Different tumor pathology and environmental factors in OSCC may have contributed to varying alteration frequencies across the studies.
2) Identify PI-3K mutations in banked OSCC tissues
Methods: In order to determine the relationship between PI-3K mutations and OSCC, computational analysis via public databases was used to select for the OSCC data (n=470;248) among numerous head and neck cancer (HNSC) studies and to explore the DNA level deviations. Additionally, the DNA of formalin-fixed and paraffin-embedded (FFPE) OSCC sections (n=28) in the Penn Medicine tissue bank was isolated to analyze for mutations of components of the PI-3K signaling pathway. The same samples were also tested for immunoreactivity to pAkt (a phosphorylated protein kinase that regulates metabolism and cell survival).
Results: Immunohistochemical methods on the samples showed Akt activation by phosphorylation in OSCC tissues. Data mining methods revealed that approximately one in five OSCC patients possessed somatic point mutations in the genes that encode for enzymes in the PI-3K pathway (e.g. PTEN, a tumor suppressor, and mTOR, a cellular response mediator). The three most frequent single nucleotide mutations for PIK3CA were H1047R, E542K, and E545K. Moreover, a third of the patients had genetic anomalies at copy number alteration (CNA) level, and frequency for loss of heterozygosity (LOH) of PTEN was approximately 40%.
Conclusions: Findings from this study show that members of the PI-3K signaling pathway are promising candidates for personalized OSCC treatments. All findings from this study are consistent with those of previous genomic and immunologic studies of HNSC or OSCC. Although PI-3K pathway activation in a subset of OSCC patients is established, there is not yet a biomarker to clinically identify them beyond extensive genomic profiling.
The LOH rate of 39% in PTEN may be significant, but until more OSCC samples are tested, it will be difficult to onnect the observation to appropriate treatment approaches. Different tumor pathology and environmental factors in OSCC may have contributed to varying alteration frequencies across the studies.