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Pedrero, J.M. et al.

Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma.

We investigated the status of the PI 3-kinase/AKT/PTEN signaling pathway in a series of 117 head and neck squamous cell carcinomas (HNSCC) in a search for molecular alterations in genes/proteins with potential prognostic value. For this purpose, PIK3CA and AKT2 gene amplification was assessed by multiplex and Quantitative Real-Time PCR. Protein expression of AKT, p-AKT, p110alpha and PTEN was determined by Western blot. PTEN allelic loss was evaluated by microsatellite analysis. PTEN-exon 5 was screened for point mutations by PCR-SSCP. Homozygous deletions were determined by multiplex PCR. PIK3CA gene was amplified in 43/117 (37%) fresh tumor samples, a frequency that did not differ from that found in archival premalignant tissues: 15/38 (39%); 12/40 (30%) fresh tumors harbored AKT2 gene amplification. AKT was found activated in 6/36 (17%) fresh tumor samples, when compared to their normal tissue counterparts. Of these 6 cases, 1 showed p110alpha overexpression and 5 displayed PTEN protein downregulation. Neither allelic loss (found in 11/77 informative cases) nor point mutations or homozygous deletions accounted for the reduced PTEN protein expression observed in our tumor series. The histologically normal mucosa of 4 patients displayed some of the molecular alterations analyzed. Dysregulation of the PI 3-K/AKT/PTEN pathway might contribute to early HNSCC tumorigenesis and might constitute a potential clinical target. Overall, 17/36 (47%) cases showed at least 1 of the molecular alterations studied here, which makes the PI 3-kinase-initiated signaling pathway one of the most frequently altered in HNSCC.[1]

References

Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma. Pedrero, J.M., Carracedo, D.G., Pinto, C.M., Zapatero, A.H., Rodrigo, J.P., Nieto, C.S., Gonzalez, M.V. Int. J. Cancer (2005) [Pubmed]

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