Abstract 569: AKT1 (E17K) mutation: coexistence with oncogenic alterations, prevalence, and correlation to clinical parameter in a large series of breast cancer patients

The AKT1 (E17K) mutation is rare and occurs in colon, ovarian, lung, and especially breast cancer where its frequency ranges between 1.4% and 8.2%. It9s precise role in cancer development and progression in clinical context is still unknown. To increase our understanding of the AKT1 (E17K) mutation in breast cancer we analyzed more than 600 tumor samples from breast cancer patients (UICC I - IV, including untreated and neoadjuvantly treated patients) which were provided by the non-profit organization PATH (Patients’ Tumor Bank of Hope, Germany). Extensive clinical data with a median follow-up time of 4.8 years to record disease progression were available for 95% of the patients included in this study. The AKT1 (E17K) mutation was detected in ∼6% of samples in the analyzed cohort using the BEAMing technology. Correlation with clinical parameters showed that the prevalence of the AKT1 (E17K) mutation was statistically independent of age or post-/pre-menopausal stage and was comparable between HER-2 positive and negative patients. In addition, FOUNDATION ONE ® targeted exome Next Generation Sequencing (NGS) analysis of some of the tumor samples was done to demonstrate the fingerprint of individual tumors in correlation with the AKT1 (E17K) mutation. NGS and BEAMing technology had a ∼98% concordance for AKT1 (E17K) mutated and non-mutated samples. In 12 out of 36 AKT1 (E17K) mutated samples no additional somatic mutations (SNVs, indels) described to drive cancer development were detected. Moreover, neither amplification nor deletion of tested genes known to be recurrently amplified or deleted in cancer were found in 10 out of these 12 samples. This supports the hypothesis that AKT1 (E17K) can be a driver mutation. However, in all of these samples mutations with yet unannotated function in additional oncogenes were detected. It remains open whether these aberrations impact the role of AKT1 (E17K) as a driver mutation in tumor growth. Analyses of patient cohort data from large databases, as demonstrated here, holds promise for discovering the role of rare somatic mutations in known oncogenes (such as AKT1 (E17K)) in the development of breast cancer. Citation Format: Marion Rudolph, Tobias Anzeneder, Matthias Ocker, Eleni Lagkadinou, Oliver Politz, Martin Michels, Anke Schulz, Georg Beckmann, Michael Teufel, Henrik Seidel, Richie Soong, Heinz Bodenmuller, Ulla Ohlms, Khusru Asadullah, Joachim Reischl. AKT1 (E17K) mutation: coexistence with oncogenic alterations, prevalence, and correlation to clinical parameter in a large series of breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 569. doi:10.1158/1538-7445.AM2014-569