Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Joshua A. Betts; Mahdi Moradi Marjaneh; Fares Al-Ejeh; Yi Chieh Lim; Wei Shi; Haran Sivakumaran; Romain Tropée; Ann Marie Patch; Michael B. Clark; Nenad Bartonicek; Adrian P. Wiegmans; Kristine M. Hillman; Susanne Kaufmann; Amanda L. Bain; Brian S. Gloss; Joanna Crawford; Stephen Kazakoff; Shivangi Wani; Shu W. Wen; Bryan Day; Andreas Möller; Nicole Cloonan; John Pearson; Melissa A. Brown; Timothy R. Mercer; Nicola Waddell; Kum Kum Khanna; Eloise Dray; Marcel E. Dinger; Stacey L. Edwards; Juliet D. French

doi:10.1016/j.ajhg.2017.07.007

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Joshua A. Betts, Mahdi Moradi Marjaneh, Fares Al-Ejeh, Yi Chieh Lim, Wei Shi, Haran Sivakumaran, Romain Tropée, Ann Marie Patch, Michael B. Clark, Nenad Bartonicek, Adrian P. Wiegmans, Kristine M. Hillman, Susanne Kaufmann, Amanda L. Bain, Brian S. Gloss, Joanna Crawford, Stephen Kazakoff, Shivangi Wani, Shu W. Wen, Bryan DayAndreas Möller, Nicole Cloonan, John Pearson, Melissa A. Brown, Timothy R. Mercer, Nicola Waddell, Kum Kum Khanna, Eloise Dray, Marcel E. Dinger, Stacey L. Edwards^*, Juliet D. French

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

73 Citations (Scopus)

Abstract

Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

Original language	English
Pages (from-to)	255-266
Number of pages	12
Journal	American Journal of Human Genetics
Volume	101
Issue number	2
DOIs	https://doi.org/10.1016/j.ajhg.2017.07.007
Publication status	Published - 3 Aug 2017
Externally published	Yes

Keywords

11q13
DNA repair
GWAS
breast cancer
enhancer
long noncoding RNAs

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10.1016/j.ajhg.2017.07.007

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Betts, J. A., Moradi Marjaneh, M., Al-Ejeh, F., Lim, Y. C., Shi, W., Sivakumaran, H., Tropée, R., Patch, A. M., Clark, M. B., Bartonicek, N., Wiegmans, A. P., Hillman, K. M., Kaufmann, S., Bain, A. L., Gloss, B. S., Crawford, J., Kazakoff, S., Wani, S., Wen, S. W., ... French, J. D. (2017). Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage. American Journal of Human Genetics, 101(2), 255-266. https://doi.org/10.1016/j.ajhg.2017.07.007

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title = "Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage",

abstract = "Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.",

keywords = "11q13, DNA repair, GWAS, breast cancer, enhancer, long noncoding RNAs",

author = "Betts, {Joshua A.} and {Moradi Marjaneh}, Mahdi and Fares Al-Ejeh and Lim, {Yi Chieh} and Wei Shi and Haran Sivakumaran and Romain Trop{\'e}e and Patch, {Ann Marie} and Clark, {Michael B.} and Nenad Bartonicek and Wiegmans, {Adrian P.} and Hillman, {Kristine M.} and Susanne Kaufmann and Bain, {Amanda L.} and Gloss, {Brian S.} and Joanna Crawford and Stephen Kazakoff and Shivangi Wani and Wen, {Shu W.} and Bryan Day and Andreas M{\"o}ller and Nicole Cloonan and John Pearson and Brown, {Melissa A.} and Mercer, {Timothy R.} and Nicola Waddell and Khanna, {Kum Kum} and Eloise Dray and Dinger, {Marcel E.} and Edwards, {Stacey L.} and French, {Juliet D.}",

note = "Publisher Copyright: {\textcopyright} 2017 American Society of Human Genetics",

year = "2017",

month = aug,

day = "3",

doi = "10.1016/j.ajhg.2017.07.007",

language = "English",

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Betts, JA, Moradi Marjaneh, M, Al-Ejeh, F, Lim, YC, Shi, W, Sivakumaran, H, Tropée, R, Patch, AM, Clark, MB, Bartonicek, N, Wiegmans, AP, Hillman, KM, Kaufmann, S, Bain, AL, Gloss, BS, Crawford, J, Kazakoff, S, Wani, S, Wen, SW, Day, B, Möller, A, Cloonan, N, Pearson, J, Brown, MA, Mercer, TR, Waddell, N, Khanna, KK, Dray, E, Dinger, ME, Edwards, SL & French, JD 2017, 'Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage', American Journal of Human Genetics, vol. 101, no. 2, pp. 255-266. https://doi.org/10.1016/j.ajhg.2017.07.007

TY - JOUR

T1 - Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

AU - Betts, Joshua A.

AU - Moradi Marjaneh, Mahdi

AU - Al-Ejeh, Fares

AU - Lim, Yi Chieh

AU - Shi, Wei

AU - Sivakumaran, Haran

AU - Tropée, Romain

AU - Patch, Ann Marie

AU - Clark, Michael B.

AU - Bartonicek, Nenad

AU - Wiegmans, Adrian P.

AU - Hillman, Kristine M.

AU - Kaufmann, Susanne

AU - Bain, Amanda L.

AU - Gloss, Brian S.

AU - Crawford, Joanna

AU - Kazakoff, Stephen

AU - Wani, Shivangi

AU - Wen, Shu W.

AU - Day, Bryan

AU - Möller, Andreas

AU - Cloonan, Nicole

AU - Pearson, John

AU - Brown, Melissa A.

AU - Mercer, Timothy R.

AU - Waddell, Nicola

AU - Khanna, Kum Kum

AU - Dray, Eloise

AU - Dinger, Marcel E.

AU - Edwards, Stacey L.

AU - French, Juliet D.

PY - 2017/8/3

Y1 - 2017/8/3

N2 - Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

AB - Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

KW - 11q13

KW - DNA repair

KW - GWAS

KW - breast cancer

KW - enhancer

KW - long noncoding RNAs

UR - http://www.scopus.com/inward/record.url?scp=85026769370&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2017.07.007

DO - 10.1016/j.ajhg.2017.07.007

M3 - Article

C2 - 28777932

AN - SCOPUS:85026769370

SN - 0002-9297

VL - 101

SP - 255

EP - 266

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 2

ER -

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

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