Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting

Hongdo Do¹^,2 , Benjamin Solomon³ , Paul L Mitchell⁴ , Stephen B Fox¹^,2 and Alexander Dobrovic¹^,2

¹Department of Pathology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Melbourne, Victoria, 8006, Australia

²Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia

³Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Melbourne, Victoria, 8006, Australia

⁴Ludwig Medical Oncology Department, Austin Hospital, Heidelberg, Victoria, 3084, Australia

author email corresponding author email

BMC Research Notes 2008, 1:14doi:10.1186/1756-0500-1-14


Published:	16 May 2008

Abstract

Background

A recurrent somatic mutation, E17K, in the pleckstrin homology domain of the AKT1 gene, has been recently described in breast, colorectal, and ovarian cancers. AKT1 is a pivotal mediator of signalling pathways involved in cell survival, proliferation and growth. The E17K mutation stimulates downstream signalling and exhibits transforming activity in vitro and in vivo.

Findings

We developed a sensitive high resolution melting (HRM) assay to detect the E17K mutation from formalin-fixed paraffin-embedded tumours. We screened 219 non-small cell lung cancer biopsies for the mutation using HRM analysis. Four samples were identified as HRM positive. Subsequent sequencing of those samples confirmed the E17K mutation in one of the cases. A rare single nucleotide polymorphism was detected in each of the remaining three samples. The E17K was found in one of the 14 squamous cell carcinomas. No mutations were found in 141 adenocarcinomas and 39 large cell carcinomas.

Conclusion

The AKT1 E17K mutation is very rare in lung cancer and might be associated with tumorigenesis in squamous cell carcinoma. HRM represents a rapid cost-effective and robust screening of low frequency mutations such as AKT1 mutations in clinical samples.