APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

Brandon Leonard; Steven N. Hart; Michael B. Burns; Michael A. Carpenter; Nuri A. Temiz; Anurag Rathore; Rachel I. Vogel; Jason B. Nikas; Emily K. Law; William L. Brown; Ying Li; Yuji Zhang; Matthew J. Maurer; Ann L. Oberg; Julie M. Cunningham; Viji Shridhar; Debra A. Bell; Craig April; David Bentley; Marina Bibikova; R. Keira Cheetham; Jian Bing Fan; Russell Grocock; Sean Humphray; Zoya Kingsbury; John Peden; Jeremy Chien; Elizabeth M. Swisher; Lynn C. Hartmann; Kimberly R. Kalli; Ellen L. Goode; Hugues Sicotte; Scott H. Kaufmann; Reuben S. Harris

doi:10.1158/0008-5472.CAN-13-1753

APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

Brandon Leonard, Steven N. Hart, Michael B. Burns, Michael A. Carpenter, Nuri A. Temiz, Anurag Rathore, Rachel I. Vogel, Jason B. Nikas, Emily K. Law, William L. Brown, Ying Li, Yuji Zhang, Matthew J. Maurer, Ann L. Oberg, Julie M. Cunningham, Viji Shridhar, Debra A. Bell, Craig April, David Bentley, Marina BibikovaR. Keira Cheetham, Jian Bing Fan, Russell Grocock, Sean Humphray, Zoya Kingsbury, John Peden, Jeremy Chien, Elizabeth M. Swisher, Lynn C. Hartmann, Kimberly R. Kalli, Ellen L. Goode, Hugues Sicotte, Scott H. Kaufmann, Reuben S. Harris

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137 Scopus citations

Abstract

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 50-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 50-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability.

Original language	English (US)
Pages (from-to)	7222-7231
Number of pages	10
Journal	Cancer Research
Volume	73
Issue number	24
DOIs	https://doi.org/10.1158/0008-5472.CAN-13-1753
State	Published - Dec 15 2013
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-13-1753

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Leonard, B., Hart, S. N., Burns, M. B., Carpenter, M. A., Temiz, N. A., Rathore, A., Vogel, R. I., Nikas, J. B., Law, E. K., Brown, W. L., Li, Y., Zhang, Y., Maurer, M. J., Oberg, A. L., Cunningham, J. M., Shridhar, V., Bell, D. A., April, C., Bentley, D., ... Harris, R. S. (2013). APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma. Cancer Research, 73(24), 7222-7231. https://doi.org/10.1158/0008-5472.CAN-13-1753

Leonard, B, Hart, SN, Burns, MB, Carpenter, MA, Temiz, NA, Rathore, A, Vogel, RI, Nikas, JB, Law, EK, Brown, WL, Li, Y, Zhang, Y, Maurer, MJ, Oberg, AL, Cunningham, JM, Shridhar, V, Bell, DA, April, C, Bentley, D, Bibikova, M, Cheetham, RK, Fan, JB, Grocock, R, Humphray, S, Kingsbury, Z, Peden, J, Chien, J, Swisher, EM, Hartmann, LC, Kalli, KR, Goode, EL, Sicotte, H, Kaufmann, SH & Harris, RS 2013, 'APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma', Cancer Research, vol. 73, no. 24, pp. 7222-7231. https://doi.org/10.1158/0008-5472.CAN-13-1753

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title = "APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma",

abstract = "Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 50-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 50-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA {"}repair{"} enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability.",

author = "Brandon Leonard and Hart, {Steven N.} and Burns, {Michael B.} and Carpenter, {Michael A.} and Temiz, {Nuri A.} and Anurag Rathore and Vogel, {Rachel I.} and Nikas, {Jason B.} and Law, {Emily K.} and Brown, {William L.} and Ying Li and Yuji Zhang and Maurer, {Matthew J.} and Oberg, {Ann L.} and Cunningham, {Julie M.} and Viji Shridhar and Bell, {Debra A.} and Craig April and David Bentley and Marina Bibikova and Cheetham, {R. Keira} and Fan, {Jian Bing} and Russell Grocock and Sean Humphray and Zoya Kingsbury and John Peden and Jeremy Chien and Swisher, {Elizabeth M.} and Hartmann, {Lynn C.} and Kalli, {Kimberly R.} and Goode, {Ellen L.} and Hugues Sicotte and Kaufmann, {Scott H.} and Harris, {Reuben S.}",

year = "2013",

month = dec,

day = "15",

doi = "10.1158/0008-5472.CAN-13-1753",

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T1 - APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

AU - Leonard, Brandon

AU - Hart, Steven N.

AU - Burns, Michael B.

AU - Carpenter, Michael A.

AU - Temiz, Nuri A.

AU - Rathore, Anurag

AU - Vogel, Rachel I.

AU - Nikas, Jason B.

AU - Law, Emily K.

AU - Brown, William L.

AU - Li, Ying

AU - Zhang, Yuji

AU - Maurer, Matthew J.

AU - Oberg, Ann L.

AU - Cunningham, Julie M.

AU - Shridhar, Viji

AU - Bell, Debra A.

AU - April, Craig

AU - Bentley, David

AU - Bibikova, Marina

AU - Cheetham, R. Keira

AU - Fan, Jian Bing

AU - Grocock, Russell

AU - Humphray, Sean

AU - Kingsbury, Zoya

AU - Peden, John

AU - Chien, Jeremy

AU - Swisher, Elizabeth M.

AU - Hartmann, Lynn C.

AU - Kalli, Kimberly R.

AU - Goode, Ellen L.

AU - Sicotte, Hugues

AU - Kaufmann, Scott H.

AU - Harris, Reuben S.

PY - 2013/12/15

Y1 - 2013/12/15

N2 - Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 50-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 50-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability.

AB - Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 50-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 50-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability.

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AN - SCOPUS:84891276148

SN - 0008-5472

VL - 73

SP - 7222

EP - 7231

JO - Cancer Research

JF - Cancer Research

IS - 24

ER -

APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

Abstract

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