Skip to main content
Download PDF

Hotspot mutation profiles of AKT1 in Asian women with breast and endometrial cancers

BMC Cancer volume 21, Article number: 1131 (2021) Cite this article

Abstract

Background

The V-Akt murine thymoma viral oncogene (AKT) 1 (E17K) is a subfamily of serine/threonine protein kinases that affects the survival, proliferation, and invasion of cancer cells. The clinicopathological features and frequencies in Asian populations with AKT1 mutations in breast and endometrial cancers are unclear. Hence, we aimed to determine the frequencies and relationships between clinicopathological features and AKT1 mutations in Asian women with cancer.

Methods

We extracted DNA from 311 and 143 samples derived from patients with breast and endometrial cancers to detect the AKT1 point mutation (hotspot), E17K. We examined correlations between clinicopathological features and AKT1 mutation status.

Results

The frequency of AKT1 mutations in breast cancer was 7.4%, and they were found more frequently in human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtypes, although this was not statistically significant (P = 0.08). The frequency of AKT1 mutations in endometrial cancer was 4.1%, and the mutations were histologically detected only in endometrioid types. However, AKT1 mutations did not correlate with relapse-free or overall survival of patients with breast or endometrial cancer.

Conclusions

AKT1 mutations are associated with HER2-negative subtype in breast cancer and in endometrial cancer with endometrioid histology. The frequencies of AKT1 mutations in breast and endometrial cancers were similar between Asian and other regional women. The frequency of mutations is too low in both tumor types to talk about predictive significance.

Peer Review reports

Background

The phosphatidylinositol 3-kinase (PI3K)/v-Akt murine thymoma viral oncogene (AKT)/mTOR pathway is activated across many cancer lineages, and it is associated with cancer development and metastasis [1]. Approximately 70% of patients with breast cancer have activated phosphatidylinositol 3-kinase (PI3K). A mutation in PI3K catalytic subunit α is one of the most frequently activated in some cancers [2].

The AKT1 subfamily of serine/threonine protein kinases affects cell survival, proliferation, and invasion. A dominant hotspot mutation is a glutamate 17 to lysine (E17K) substitution, and AKT1 pleckstrin homology domain mutations activate serine-threonine kinase. Moreover, the findings of recent clinical trials have suggested that mutated AKT1 is a potent predictive marker of responses to AKT inhibitors [3, 4].

A large-scale retrospective analysis of recent data derived from ~ 20,000 solid tumours revealed an AKT1 mutation frequency of ~ 1% [1]. The reported frequencies of AKT1 mutations are between 1.4 and 8.2% [5, 6] in breast cancer and 2.2 and 4.1% in endometrial cancer [7, 8].

However, the clinicopathological features and mutation frequency of AKT1 in Asian populations with breast and endometrial cancers have not been examined. Here, we investigated the frequencies of AKT1 mutations and their associations with clinicopathological features in Asian women with breast and endometrial cancers.

Materials and methods

The pathological and clinical data of the cases used in this study were collected from the medical records in a retrospective manner.

Tissue samples and patient selection

Breast cancer cohort

We obtained 118 frozen tumour surgical specimens and 193 formalin-fixed paraffin-embedded (FFPE) surgical or biopsy tissues that had been preserved in a biobank at the National Cancer Centre Hospital between May 1989 and December 2012. We extracted DNA from the frozen tumour specimens and FFPE tissues using QIAamp DNA Mini Kits and QIAamp DNA FFPE Tissue Kits, respectively (Qiagen GmbH, Hilden, Germany) as described by the manufacturer [9]. Mutations at the AKT1 hotspot detected using peptide nucleic acid-locked nucleic acid (PNA-LNA) clamp methods in samples collected and stored at the National Cancer Center Hospital were analysed by LSI Medience Corporation (Tokyo, Japan) as described previously [10].

Endometrial cancer cohort

We extracted DNA from 142 DNA FFPE surgical tissue samples that had been preserved at the National Cancer Centre Hospital between May 1989 and November 2012 using QIAamp DNA FFPE Tissue Kits (Qiagen) as described by the manufacturer [9]. We detected the AKT1 hotspot mutation using real-time PCR as described [8] with the forward and reverse primer sequences of exon 4 of AKT1 (5′-CACACCCAGTTCCTGCCTG-3′ and 5′-CCTGGTGGGCAAAGAGGGCT-3′, respectively). The PCR cycling program comprised activation at 94 °C for 5 min, followed by 35 cycles at 94 °C for 30 s, 55 °C for 30 s, 72 °C for 60 s, and 72 °C for 10 min. The PCR products were sequenced using the BigDye terminator method and an auto-sequencer (Applied Biosystems, Foster City, CA, USA).

Histopathological evaluation

Oestrogen (ER) or progesterone (PgR) receptors were classified as positive or negative based on ASCO/CAP Guideline [11]. In all cases, at least 1% of cells staining was considered positive according to the criteria. Human epidermal growth factor receptor-2 (HER2) positivity was classified according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists [12]. Hormone receptor-positive status was defined as positive for either ER or PgR. The histological and nuclear grade of breast cancer and endometrioid uterine carcinoma were graded as described in previous studies [9, 13] and in a previous report [14], respectively. Pathological evaluations are always performed by at least two expert pathologists (including HY and MY), although the results of diagnoses in institutional practice are used. ND in our Tables is because there was a time when it was not evaluated in the old days, and we could not re-evaluate it sufficiently because of the deterioration of pathological specimens.

Clinical outcome evaluation based on AKT1 mutation

Differences in outcomes between patients with and without AKT1 mutations were assessed using data from 311 and 143 patients in breast and endometrial cancer subgroups. Differences between proportions for categorical variables were analysed using chi-square tests. Postoperative relapse-free (RFS) and overall (OS) survival was analysed using Kaplan–Meier curves. We defined RFS as elapsed time between the day of surgery and disease progression or the last follow-up for operable lesions. We defined OS as elapsed time between the first day of diagnosis and the date of death or the last follow-up. Significant prognostic factors associated with RFS and OS were determined by multivariate analysis using Cox hazard models. Clinically relevant factors for breast (initial stage, histologic grade, ER status, PgR status, HER2 status, and AKT1 mutation) and endometrial (diagnostic stage, lymphovascular invasion, and AKT1 mutations) cancers were included as covariates in multiple Cox proportional hazards models. All data were statistically analysed using JMP version 11 (SAS Institute, Cary, NC, USA). Statistical significance was set at P < 0.05.

Results

Prevalence of AKT1 hotspot mutation (E17K) in patients with breast cancer

The overall prevalence of AKT1 mutations was 23 (7.4%) of 311 breast cancer samples.

Association of AKT1 mutation with clinicopathological parameters in breast cancer

Table 1 shows the clinicopathological parameters according to AKT1 mutations in the breast cancer samples. Mutated AKT1 was not associated with prevalence, age, histologic subtype, initial stage (7th edition of UICC [the Union for International Cancer Control] TNM stage), tumour grade, lymphovascular invasion, and hormone receptor status. In the 16 patients with the so-called triple negative subtype, which is negative for both ER/PgR/HER2, two patients had AKT1 hotspot mutations. The number of patients with AKT1 hotspot mutation was 13% (3/22). On the other hand, HER2-negative status tended to have more AKT1 gene mutations, although this was not statistically significant (P = 0.08).

Table 1 Characteristics of Asian patients with breast cancer (N = 311)
Full size table

The median follow-up duration was 73 (range 2.5–450) months. Twenty-eight patients initially had metastases, 148 of the 283 patients who initially had early breast cancer relapsed (137 and 11 with wild-type and AKT1 mutations, respectively), and 48 died of breast cancer.

The RFS and OS did not significantly differ between patients with wild-type and mutated AKT1 (Fig. 1). The median relapse-free durations in patients with mutated and wild-type AKT1 were 75 and 79 months, respectively (P = 0.77). Multivariate analysis associated only the initial stage with OS (Additional Table 1).

Fig. 1
figure 1

Relapse-free survival (RFS) and overall survival (OS) in patients with breast cancer. There were no significant differences in RFS and OS between patients with wild-type AKT1 breast cancer and those with AKT1-mutated breast cancer

Full size image

Prevalence of AKT1 hotspot mutations (E17K) in patients with endometrial cancer

The overall prevalence of mutated AKT1 in endometrial cancer samples was 6 (4.1%) of 143 (Additional Figure 1).

Associations between AKT1 mutation with clinicopathological parameters in endometrial cancer

Table 2 shows the clinicopathological parameters according to AKT1 mutations in the endometrial cancer samples. Mutated AKT1 was not associated with prevalence and age, histological subtype, initial stage (UICC 8th ed. /FIGO 2018), tumour grade in the histological subtype, or lymphovascular invasion.

Table 2 Characteristics of Asian patients with endometrial cancer (N = 143)
Full size table

The median follow-up duration was 60 (range 0.6–275) months. Six patients initially had metastatic lesions, 18 of the 137 patients who initially had early endometrial cancer, relapsed (16 and 2 patients with wild-type and mutated AKT1, respectively), and 21 patients died of any cause. Three deaths were related to other types of cancer or other diseases, and 18 were due to endometrial cancer.

The RFS and OS did not significantly differ between patients with wild-type and mutated AKT1 (Fig. 2). The median RFS in patients with mutated and wild-type AKT1 were 77.8 months and not reached, respectively (P = 0.13). The median OS in patients with mutated and wild-type AKT1 was not reached and 183 months, respectively (P = 0.21). Multivariate analysis associated the initial stage and AKT1 mutation with OS (Additional Table 2).

Fig. 2
figure 2

Relapse-free survival (RFS) and overall survival (OS) in patients with endometrial cancer. There were no significant differences in RFS and OS between patients with wild-type AKT1 endometrial cancer and those with AKT1-mutated endometrial cancer

Full size image

Discussion

This is the first report of an association between clinicopathological features and AKT1 mutation status in women with breast and endometrial cancers in Asia.

In the present study, we found AKT1 mutations in 7.3 and 4.1% of breast and of endometrial cancer samples. The reported frequency of AKT1 mutations in breast cancer is between 1.4 and 8.2% [5, 6], and they are associated with histogenesis of hormone receptor positive subtype [15]. Thus, our finding that AKT1 mutations are associated with HER2-negative status in breast cancer agrees with those of a previous study [15]. The TCGA (The Cancer Genome Atlas Program) data showed that in a predominantly Caucasian breast cancer cohort, AKT1 mutations had a frequency of 3% in most hormone receptor positive breast cancers [16]. On the other hand, a report from China also showed that AKT1 mutations were found in 7.1 and 8.2% of breast cancer patients [6, 17], suggesting that AKT1 mutations may be particularly common in Asians.

Previous reports have suggested that activation of the PI3K/AKT pathway is involved in the development of endometrioid adenocarcinoma [7, 8, 18], and that atypical hyperplasia is also associated with AKT1 mutations, leading to benign and (pre) malignant endometrial lesions [19]. In addition, AKT1 mutations were found in atypical hyperplasia, suggesting that AKT1 mutations may be involved in the carcinogenesis of endometrial carcinoma in benign and (pre) malignant endometrial lesions [19]. Louis J.M. van der Putten et al. reported We did not find a relationship between clinicopathological features and AKT1 mutations because of the rarity of the mutation. However, none of the patients with mutated AKT1 died. A longer follow-up might reveal a correlation between AKT1 mutation status and its prognostic importance.

Our survival results themselves are difficult to say definitively due to the small number of cases. However, recently published results from the AACR Project GENIE, which incorporated a large group of estrogen receptor positive breast cancer patients, reported that AKT1 mutant cases had comparable survival rates compared to AKT1 wild-type controls [20].

Despite these positive findings, this study has three major limitations. The AKT1 mutation is rare, and rates of relapse or death are extremely low. Therefore, we cannot reach any conclusions on the survival based on prognostic factors. Recently, with the development of next generation sequencing (NGS), cancer genomic profiling including AKT1 are now being evaluated using NGS tests. It is an important limitation that this study only examined AKT1 E17K hotspot mutation. Finally, there is fact that a large proportion of endometrial cancer is associated with a hypermutator phenotype, mainly due to MSI (microsatellite instability) and POLE (DNA polymerase epsilon) mutations. It is hard to distinguish the real AKT1 driver mutations from random mutations caused by this phenotype.

Precision medicine is becoming important in the treatment of cancer, and the AKT1 mutation is a promising target. Active point mutations (hot spots), are limited in breast and endometrial cancers, and E17K is a representative mutation site. The development of systems for detecting single mutations has progressed. Moreover, recent clinical trials have suggested that the AKT1 mutation is a potent predictive marker of a response to AKT inhibitors [3, 4]. Therefore, the AKT1 mutation might be a target of liquid biopsies, particularly in cell-free plasma DNA [21].

In conclusion, the rate of mutated AKT1 in breast cancer was 7.4%, and it correlated with the HER2-negative subtype. The rate in endometrial cancer was 4.1%. AKT1 mutations are associated with HER2-negative subtype in breast cancer and in endometrial cancer with endometrioid histology. The frequencies of AKT1 mutations in breast and endometrial cancers were similar between Asian and other regional women. The frequency of mutations is too low in both tumor types to talk about predictive significance.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Akt:

V-Akt murine thymoma viral oncogene

Bp:

partial mastectomy

Bt:

total mastectomy

ER:

oestrogen receptor

FFPE:

formalin-fixed paraffin-embedded

HER2:

human epidermal growth factor receptor-2

HR:

hormone receptor

IDC:

invasive ductal carcinoma

ILC:

invasive lobular carcinoma

LVI:

lymphovascular invasion

mut:

mutation

ND:

no data

PgR:

progesterone receptor

References

  1. Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009;4:127–50. https://doi.org/10.1146/annurev.pathol.4.110807.092311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol. 2013;10(3):143–53. https://doi.org/10.1038/nrclinonc.2013.10.

    Article  CAS  PubMed  Google Scholar 

  3. Davies BR, Guan N, Logie A, Crafter C, Hanson L, Jacobs V, et al. Tumors with AKT1 E17K mutations are rational targets for single agent or combination therapy with AKT inhibitors. Mol Cancer Ther. 2015;14(11):2441–51. https://doi.org/10.1158/1535-7163.MCT-15-0230.

    Article  CAS  PubMed  Google Scholar 

  4. Tamura K, Hashimoto J, Tanabe Y, Kodaira M, Yonemori K, Seto T, et al. Safety and tolerability of AZD5363 in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016;77(4):787–95. https://doi.org/10.1007/s00280-016-2987-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Millis SZ, Ikeda S, Reddy S, Gatalica Z, Kurzrock R. Landscape of phosphatidylinositol-3-kinase pathway alterations across 19 784 diverse solid tumors. JAMA Oncol. 2016;2(12):1565–73. https://doi.org/10.1001/jamaoncol.2016.0891.

    Article  PubMed  Google Scholar 

  6. Troxell ML. Clinical & experimental pathology PIK3CA/AKT1 mutations in breast carcinoma: a comprehensive review of experimental and clinical studies. J Clin Exp Pathol. 2012;S1:1–11.

    Google Scholar 

  7. Cohen Y, Shalmon B, Korach J, Barshack I, Fridman E, Rechavi G. AKT1 pleckstrin homology domain E17K activating mutation in endometrial carcinoma. Gynecol Oncol. 2010;116(1):88–91. https://doi.org/10.1016/j.ygyno.2009.09.038.

    Article  CAS  PubMed  Google Scholar 

  8. Shoji K, Oda K, Nakagawa S, Hosokawa S, Nagae G, Uehara Y, et al. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Br J Cancer. 2009;101(1):145–8. https://doi.org/10.1038/sj.bjc.6605109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shimoi T, Hamada A, Yamagishi M, Hirai M, Yoshida M, Nishikawa T, et al. PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system. Cancer Sci. 2018;109(8):2558–66. https://doi.org/10.1111/cas.13696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Watanabe K, Fukuhara T, Tsukita Y, Morita M, Suzuki A, Tanaka N, et al. EGFR mutation analysis of circulating tumor DNA using an improved PNA-LNA PCR clamp method. Can Respir J. 2016;2016:5297329.

    Article  Google Scholar 

  11. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL. Estrogen and progesterone receptor testing in breast Cancer: ASCO/CAP guideline update. J Clin Oncol. 2020 Apr 20;38(12):1346–66. https://doi.org/10.1200/JCO.19.02309.

    Article  PubMed  Google Scholar 

  12. Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

  13. Shimoi T, Yoshida M, Kitamura Y, Yoshino T, Kawachi A, Shimomura A, et al. TERT promoter hotspot mutations in breast cancer. Breast Cancer. 2018;25(3):292–6. https://doi.org/10.1007/s12282-017-0825-5.

    Article  PubMed  Google Scholar 

  14. Yunokawa M, Yoshida H, Watanabe R, Noguchi E, Shimomura A, Shimoi T, et al. Allred score is a promising predictor of prognosis and medroxyprogesterone acetate efficacy in patients with endometrial cancer. Cancer Chemother Pharmacol. 2017;80(1):127–34. https://doi.org/10.1007/s00280-017-3342-5.

    Article  CAS  PubMed  Google Scholar 

  15. Beaver JA, Gustin JP, Yi KH, Rajpurohit A, Thomas M, Gilbert SF, et al. PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model system. Clin Cancer Res. 2013;19(19):5413–22. https://doi.org/10.1158/1078-0432.CCR-13-0884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.

    Article  Google Scholar 

  17. Wen L, Zhang G, Ren C, Li X, Mok H, Jia M, et al. Characterization of AKT somatic mutations in Chinese breast Cancer patients. Cancer Manag Res. 2021 Apr 7;13:3055–65. https://doi.org/10.2147/CMAR.S299624.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67–73.

    Article  Google Scholar 

  19. van der Putten LJM, van Hoof R, Tops BBJ, Snijders MPLM, van den Berg-van Erp SH, van der Wurff AAM, et al. Molecular profiles of benign and (pre) malignant endometrial lesions. Carcinogenesis. 2017 Mar 1;38(3):329–35. https://doi.org/10.1093/carcin/bgx008.

    Article  CAS  PubMed  Google Scholar 

  20. Smyth LM, Zhou Q, Nguyen B, Yu C, Lepisto EM, Arnedos M. Characteristics and outcome of AKT1 E17K-mutant breast Cancer defined through AACR project GENIE, a Clinicogenomic registry. Cancer Discov. 2020 Apr;10(4):526–35. https://doi.org/10.1158/2159-8290.CD-19-1209 Epub 2020 Jan 10.

  21. Hyman DM, Smyth LM, Donoghue MTA, Westin SN, Bedard PL, Dean EJ, et al. AKT inhibition in solid tumors with AKT1 mutations. J Clin Oncol. 2017;35(20):2251–9. https://doi.org/10.1200/JCO.2017.73.0143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We are grateful to Yukiko Shimada, Yuka Kitamura, and Tomomi Yoshino for technical support, and Ms. Onozawa and Nakamura for administrative assistance throughout this study. We sincerely thank all the patients who provided tissue samples.

Funding

This study was supported by the Cancer Research and Development [− 15 - B 23] Fund of the Ministry of Health, Labour and Welfare.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Tatsunori Shimoi, Jun Hashimoto, Kazuki Sudo, Emi Noguchi, Kan Yonemori, Yasuhiro Fujiwara & Kenji Tamura

  2. Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, 3-1-3 Hongoh, Bunkyo-ku, Tokyo, 113-0033, Japan

    Tatsunori Shimoi, Jun Hashimoto & Takahiro Fukuda

  3. Division of Medical Oncology, Department of Internal Medicine, St. Lukes International Hospital, Tokyo, Japan

    Jun Hashimoto

  4. Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan

    Akihiko Shimomura & Chikako Shimizu

  5. Department of Gynecologic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Mayu Yunokawa

  6. Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan

    Hiroshi Yoshida & Masayuki Yoshida

  7. Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan

    Tomoyasu Kato

  8. Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan

    Takayuki Kinoshita

  9. Division of Breast Surgery, Tokyo Medical Center, Tokyo, Japan

    Takayuki Kinoshita

  10. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  11. Innovative Cancer Center, Department of Medical Oncology, Shimane University Hospital, Shimane, Japan

    Kenji Tamura

Authors
  1. Tatsunori Shimoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuki Sudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akihiko Shimomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emi Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chikako Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mayu Yunokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kan Yonemori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroshi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masayuki Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tomoyasu Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takayuki Kinoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Takahiro Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yasuhiro Fujiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kenji Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TS designed the study, TS and JH collected the data. TS statistically analyzed the data. TS, JH, KS, AS, EN, CS, MYunokawa, KY, HY, MYoshida, TKato, TKinoshita, TF, YF and KT drafted the manuscript and read and approved the final version for publication. TS and JH contributed equally to the study, and all authors significantly contributed to the content of the manuscript.

Corresponding author

Correspondence to Tatsunori Shimoi.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the National Cancer Center Research Ethics Review Committee at the National Cancer Center Hospital, Tokyo, Japan (approval No. 2014 092). This study was conducted in accordance with the Declaration of Helsinki (2013). The requirement for informed consent was waived by the Institutional Review Board of the National Cancer Center Hospital, owing to the retrospective nature of the study. Patients could refuse to participate in this study in an opt-out form on the website of our institution.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shimoi, T., Hashimoto, J., Sudo, K. et al. Hotspot mutation profiles of AKT1 in Asian women with breast and endometrial cancers. BMC Cancer 21, 1131 (2021). https://doi.org/10.1186/s12885-021-08869-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12885-021-08869-3

Keywords

BMC Cancer

ISSN: 1471-2407

Contact us