Peer Reviewed

1

Document Type

Article

Publication Date

11-8-2016

Keywords

AKT1 E17K mutation, Blood-based mutation detection, Breast cancer

Funder/Sponsor

Science Foundation Ireland. Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT. European Union’s Seventh Framework Programme

Comments

The original article is available at www.biomedcentral.com

Abstract

BACKGROUND: The single hotspot mutation AKT1 [G49A:E17K] has been described in several cancers, with the highest incidence observed in breast cancer. However, its precise role in disease etiology remains unknown.

METHODS: We analyzed more than 600 breast cancer tumor samples and circulating tumor DNA for AKT1 (E17K) and alterations in other cancer-associated genes using Beads, Emulsions, Amplification, and Magnetics digital polymerase chain reaction technology and targeted exome sequencing.

RESULTS: Overall AKT1 (E17K) mutation prevalence was 6.3 % and not correlated with age or menopausal stage. AKT1 (E17K) mutation frequency tended to be lower in patients with grade 3 disease (1.9 %) compared with those with grade 1 (11.1 %) or grade 2 (6 %) disease. In two cohorts of patients with advanced metastatic disease, 98.0 % (n = 50) and 97.1 % (n = 35) concordance was obtained between tissue and blood samples for the AKT1 (E17K) mutation, and mutation capture rates of 66.7 % (2/3) and 85.7 % (6/7) in blood versus tissue samples were observed. Although AKT1-mutant tumor specimens were often found to harbor concurrent alterations in other driver genes, a subset of specimens harboring AKT1 (E17K) as the only known driver alteration was also identified. Initial follow-up survival data suggest that AKT1 (E17K) could be associated with increased mortality. These findings warrant additional long-term follow-up.

CONCLUSIONS: The data suggest that AKT1 (E17K) is the most likely disease driver in certain breast cancer patients. Blood-based mutation detection is achievable in advanced-stage disease. These findings underpin the need for a further enhanced-precision medicine paradigm in the treatment of breast cancer.

Disciplines

Physics | Physiology

Citation

Rudolph M, Anzeneder T, Schulz A, Beckmann G, Byrne AT, Jeffers M, Pena C, Politz O, Köchert K, Vonk R, Reischl J. AKT1 (E17K) mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection. BMC Cancer. 2016;16:622

PubMed ID

27515171

DOI Link

10.1186/s12885-016-2626-1

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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