APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers.
The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
S
S
Kondo
Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
K
K
Wakae
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
N
N
Wakisaka
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Y
Y
Nakanishi
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
K
K
Ishikawa
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
T
T
Komori
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
M
M
Moriyama-Kita
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
K
K
Endo
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
S
S
Murono
Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.|Division of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Z
Z
Wang
Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
K
K
Kitamura
Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
T
T
Nishiyama
Functional Genomic Facility, National Institute of Basic Biology, Myodaiji, Okazaki, Japan.
K
K
Yamaguchi
Functional Genomic Facility, National Institute of Basic Biology, Myodaiji, Okazaki, Japan.
S
S
Shigenobu
Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
M
M
Muramatsu
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
T
T
Yoshizaki
D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016679:Genome, Viral; D006801:Humans; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000209:etiology* / Q000378:metabolism*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000502:physiology*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D011506:Proteins; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2246-51
23341589
Nature. 2013 Feb 21;494(7437):366-70
23389445
PLoS Pathog. 2013;9(5):e1003361
23696735
J Virol. 2009 Sep;83(18):9474-85
19587057
J Clin Microbiol. 2002 Mar;40(3):863-7
11880406
PLoS One. 2014 May 23;9(5):e97787
24858917
J Gen Virol. 2007 Feb;88(Pt 2):432-40
17251560
J Clin Oncol. 2011 Nov 10;29(32):4294-301
21969503
N Engl J Med. 2001 Apr 12;344(15):1125-31
11297703
Retrovirology. 2008 Jun 24;5:51
18577210
BMC Biotechnol. 2008 Jul 24;8:57
18652663
Nat Struct Mol Biol. 2010 Feb;17(2):222-9
20062055
Cell. 2003 Jun 13;113(6):803-9
12809610
Nature. 2013 Jul 11;499(7457):214-8
23770567
Cancer Res. 1995 Nov 15;55(22):5465-71
7585617
Cell Rep. 2014 Jun 26;7(6):1833-41
24910434
Nature. 2007 Feb 22;445(7130):927-30
17259974
J Virol. 2011 Nov;85(21):11255-64
21849440
Hepatology. 2006 Jun;43(6):1364-74
16729314
DNA Repair (Amst). 2014 Jul;19:38-47
24746924
Nat Genet. 2013 Sep;45(9):977-83
23852168
Int J Cancer. 2007 Apr 1;120(7):1418-25
17205528
PLoS One. 2013 Apr 25;8(4):e62066
23634222
Proc Natl Acad Sci U S A. 2005 Jun 7;102(23 ):8321-6
15919829
J Virol. 2014 Jan;88(2):1308-17
24227842
Trends Microbiol. 2011 Jan;19(1):33-9
21050765
Cell Rep. 2016 Feb 16;14 (6):1273-82
26832400
Elife. 2013 Apr 16;2:e00534
23599896
J Virol. 2011 Oct;85(19):9726-36
21775448
Nat Rev Cancer. 2002 May;2(5):342-50
12044010
Nature. 2013 Aug 22;500(7463):415-21
23945592
Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):675-87
19038776
J Clin Oncol. 2013 Dec 20;31(36):4550-9
24248688
Cell. 2012 May 25;149(5):979-93
22608084
Science. 2008 Apr 11;320(5873):230-3
18403710
J Virol. 2011 Feb;85(4):1765-76
21123384
Cancer Prev Res (Phila). 2011 Feb;4(2):207-17
21292634
EMBO Rep. 2011 May;12(5):444-50
21460793
J Gen Virol. 2005 Jan;86(Pt 1):125-9
15604439
J Virol. 2015 Jan;89(1):688-702
25355878
Cell. 2000 Sep 1;102(5):553-63
11007474
J Virol. 2008 Jul;82(14 ):6852-61
18480459
Am J Pathol. 1998 Jan;152(1):145-56
9422532
PLoS One. 2013 Aug 20;8(8):e73641
23977391
Virology. 2007 Oct 25;367 (2):440-51
17631933
Nat Rev Cancer. 2014 Dec;14 (12 ):786-800
25568919
Nat Genet. 2013 Sep;45(9):970-6
23852170
J Virol. 2011 Aug;85(15):7594-602
21632763
J Pathol. 2007 Aug;212(4):356-67
17573670
J Natl Cancer Inst. 2000 May 3;92(9):709-20
10793107
Nat Rev Immunol. 2004 Nov;4(11):868-77
15516966