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Published in: Breast Cancer 5/2016

01-09-2016 | Original Article

APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers

Authors: Miki Tsuboi, Arito Yamane, Jun Horiguchi, Takehiko Yokobori, Reika Kawabata-Iwakawa, Shinji Yoshiyama, Susumu Rokudai, Hiroki Odawara, Hideaki Tokiniwa, Tetsunari Oyama, Izumi Takeyoshi, Masahiko Nishiyama

Published in: Breast Cancer | Issue 5/2016

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Abstract

Background

The members of AID/APOBEC protein family possess cytidine deaminase activity that converts cytidine residue to uridine on DNA and RNA. Recent studies have shown the possible influence of APOBEC3B (A3B) as DNA mutators of breast cancer genome. However, the clinical significance of A3B expression in Japanese breast cancer has not been studied in detail.

Methods

Ninety-three primary breast cancer tissues (74 estrogen-receptor (ER) positive, 3 ER and HER2 positive, 6 HER2 positive, and 10 triple negative) including 37 tumor-normal pairs were assessed for A3B mRNA expression using quantitative real-time RT-PCR. We analyzed the relation between A3B expression, mutation analysis of TP53 and PIK3CA by direct sequencing, polymorphic A3B deletion allele and human papillomavirus (HPV) infection in tumors.

Results

A3B mRNA was overexpressed in tumors compared with normal tissue. Patients with high A3B expression were associated with subtype and progression of lymph node metastasis and pathological nuclear grade. However, the expression was not related to any other clinicopathological factors, including mutation of TP53 and PIK3CA, polymorphic A3B deletion allele, HPV infection and survival time.

Conclusion

The expression of A3B in breast cancer was higher than in non-cancerous tissues and was related to the lymph node metastasis and nuclear grade, which are reliable aggressive phenotype markers in breast cancer. Evaluation of A3B expression in tumor may be a marker for breast cancer with malignant potential.
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Literature
2.
go back to reference Helleday T, Eshtad S, Nik-Zainal S. Mechanisms underlying mutational signatures in human cancers. Nat Rev Genet. 2014;15:585–98.CrossRefPubMed Helleday T, Eshtad S, Nik-Zainal S. Mechanisms underlying mutational signatures in human cancers. Nat Rev Genet. 2014;15:585–98.CrossRefPubMed
3.
go back to reference Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, et al. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature. 2013;494:366–70.CrossRefPubMedPubMedCentral Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, et al. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature. 2013;494:366–70.CrossRefPubMedPubMedCentral
5.
go back to reference Mori S, Takeuchi T, Ishii Y, Kukimoto I. Identification of APOBEC3B promoter elements responsible for activation by human papillomavirus type 16 E6. Biochem Biophys Res Commun. 2015;460:555–60.CrossRefPubMed Mori S, Takeuchi T, Ishii Y, Kukimoto I. Identification of APOBEC3B promoter elements responsible for activation by human papillomavirus type 16 E6. Biochem Biophys Res Commun. 2015;460:555–60.CrossRefPubMed
6.
go back to reference Sieuwerts AM, Willis S, Burns MB, Look MP, Gelder ME, Schlicker A, et al. Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers. Horm Cancer. 2014;5:405–13.CrossRefPubMedPubMedCentral Sieuwerts AM, Willis S, Burns MB, Look MP, Gelder ME, Schlicker A, et al. Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers. Horm Cancer. 2014;5:405–13.CrossRefPubMedPubMedCentral
7.
go back to reference Bhoo-Pathy N, Yip CH, Hartman M, Uiterwaal CS, Devi BC, Peeters PH, et al. Breast cancer research in Asia: adopt or adapt Western knowledge? Eur J Cancer. 2013;49:703–9.CrossRefPubMed Bhoo-Pathy N, Yip CH, Hartman M, Uiterwaal CS, Devi BC, Peeters PH, et al. Breast cancer research in Asia: adopt or adapt Western knowledge? Eur J Cancer. 2013;49:703–9.CrossRefPubMed
8.
go back to reference Maskarinec G, Sen C, Koga K, Conroy SM. Ethnic differences in breast cancer survival: status and determinants. Womens Health (Lond Engl). 2011;7:677–87.CrossRef Maskarinec G, Sen C, Koga K, Conroy SM. Ethnic differences in breast cancer survival: status and determinants. Womens Health (Lond Engl). 2011;7:677–87.CrossRef
9.
go back to reference Iqbal J, Ginsburg O, Rochon PA, Sun P, Narod SA. Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States. JAMA. 2015;313:165–73.CrossRefPubMed Iqbal J, Ginsburg O, Rochon PA, Sun P, Narod SA. Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States. JAMA. 2015;313:165–73.CrossRefPubMed
10.
11.
go back to reference Komatsu A, Nagasaki K, Fujimori M, Amano J, Miki Y. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol. 2008;33:261–70.PubMed Komatsu A, Nagasaki K, Fujimori M, Amano J, Miki Y. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol. 2008;33:261–70.PubMed
12.
go back to reference Long J, Delahanty RJ, Li G, Gao YT, Lu W, Cai Q, et al. A common deletion in the APOBEC3 genes and breast cancer risk. J Natl Cancer Inst. 2013;105:573–9.CrossRefPubMedPubMedCentral Long J, Delahanty RJ, Li G, Gao YT, Lu W, Cai Q, et al. A common deletion in the APOBEC3 genes and breast cancer risk. J Natl Cancer Inst. 2013;105:573–9.CrossRefPubMedPubMedCentral
13.
go back to reference Caval V, Suspene R, Shapira M, Vartanian JP, Wain-Hobson S. A prevalent cancer susceptibility APOBEC3A hybrid allele bearing APOBEC3B 3′UTR enhances chromosomal DNA damage. Nat Commun. 2014;5:5129.CrossRefPubMed Caval V, Suspene R, Shapira M, Vartanian JP, Wain-Hobson S. A prevalent cancer susceptibility APOBEC3A hybrid allele bearing APOBEC3B 3′UTR enhances chromosomal DNA damage. Nat Commun. 2014;5:5129.CrossRefPubMed
14.
go back to reference Imahashi M, Izumi T, Watanabe D, Imamura J, Matsuoka K, Ode H, et al. Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk. PLoS One. 2014;9:e92861.CrossRefPubMedPubMedCentral Imahashi M, Izumi T, Watanabe D, Imamura J, Matsuoka K, Ode H, et al. Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk. PLoS One. 2014;9:e92861.CrossRefPubMedPubMedCentral
15.
go back to reference Li N, Bi X, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and sporadic breast carcinoma risk: a meta-analysis. Breast Cancer Res Treat. 2011;126:515–20.CrossRefPubMed Li N, Bi X, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and sporadic breast carcinoma risk: a meta-analysis. Breast Cancer Res Treat. 2011;126:515–20.CrossRefPubMed
17.
go back to reference Akhter J, Ali Aziz MA, Al Ajlan A, Tulbah A, Akhtar M. Breast cancer: is there a viral connection? Adv Anat Pathol. 2014;21:373–81.CrossRefPubMed Akhter J, Ali Aziz MA, Al Ajlan A, Tulbah A, Akhtar M. Breast cancer: is there a viral connection? Adv Anat Pathol. 2014;21:373–81.CrossRefPubMed
18.
go back to reference Vernet-Tomas M, Mena M, Alemany L, Bravo I, De Sanjose S, Nicolau P, et al. Human papillomavirus and breast cancer: no evidence of association in a Spanish set of cases. Anticancer Res. 2015;35:851–6.PubMed Vernet-Tomas M, Mena M, Alemany L, Bravo I, De Sanjose S, Nicolau P, et al. Human papillomavirus and breast cancer: no evidence of association in a Spanish set of cases. Anticancer Res. 2015;35:851–6.PubMed
19.
go back to reference Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012;486:405–9.CrossRefPubMedPubMedCentral Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012;486:405–9.CrossRefPubMedPubMedCentral
20.
go back to reference Bertheau P, Lehmann-Che J, Varna M, Dumay A, Poirot B, Porcher R, et al. p53 in breast cancer subtypes and new insights into response to chemotherapy. Breast. 2013;22(Suppl 2):S27–9.CrossRefPubMed Bertheau P, Lehmann-Che J, Varna M, Dumay A, Poirot B, Porcher R, et al. p53 in breast cancer subtypes and new insights into response to chemotherapy. Breast. 2013;22(Suppl 2):S27–9.CrossRefPubMed
21.
go back to reference Niikura N, Sakatani T, Arima N, Ohi Y, Honma N, Kanomata N et al. Assessment of the Ki67 labeling index: a Japanese validation ring study. Breast Cancer. 2014. Niikura N, Sakatani T, Arima N, Ohi Y, Honma N, Kanomata N et al. Assessment of the Ki67 labeling index: a Japanese validation ring study. Breast Cancer. 2014.
Metadata
Title
APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers
Authors
Miki Tsuboi
Arito Yamane
Jun Horiguchi
Takehiko Yokobori
Reika Kawabata-Iwakawa
Shinji Yoshiyama
Susumu Rokudai
Hiroki Odawara
Hideaki Tokiniwa
Tetsunari Oyama
Izumi Takeyoshi
Masahiko Nishiyama
Publication date
01-09-2016
Publisher
Springer Japan
Published in
Breast Cancer / Issue 5/2016
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-015-0641-8

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