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

被引：35

作者：

Do H. ^{[1
,2
]}

Solomon B. ^{[3
]}

Mitchell P.L. ^{[4
]}

Fox S.B. ^{[1
,2
]}

Dobrovic A. ^{[1
,2
]}

机构：

[1] Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC 8006, Locked Bag 1, A'Beckett St

[2] Department of Pathology, University of Melbourne, Parkville

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

[4] Ludwig Medical Oncology Department, Austin Hospital, Heidelberg

来源：

BMC Research Notes | / 1卷 / 1期

基金：

英国医学研究理事会;

关键词：

High Resolution Melting; Large Cell Carcinoma; Pleckstrin Homology Domain; E17K Mutation; High Resolution Melting Analysis;

D O I：

10.1186/1756-0500-1-14

中图分类号：

学科分类号：

摘要：

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. © 2008 Do et al; licensee BioMed Central Ltd.

引用

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