Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents. / Birkbak, Nicolai J.; Wang, Zhigang C.; Kim, Ji-Young; Eklund, Aron C.; Li, Qiyuan; Tian, Ruiyang; Bowman-Colin, Christian; Li, Yang; Greene-Colozzi, April; Iglehart, J. Dirk; Tung, Nadine; Ryan, Paula D.; Garber, Judy E.; Silver, Daniel P.; Szallasi, Zoltan; Richardson, Andrea L.

In: Cancer Drug Discovery and Development, Vol. 2, No. 4, 2012, p. 366-375.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

Harvard

Birkbak, NJ, Wang, ZC, Kim, J-Y, Eklund, AC, Li, Q, Tian, R, Bowman-Colin, C, Li, Y, Greene-Colozzi, A, Iglehart, JD, Tung, N, Ryan, PD, Garber, JE, Silver, DP, Szallasi, Z & Richardson, AL 2012, 'Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents' Cancer Drug Discovery and Development, vol 2, no. 4, pp. 366-375., 10.1158/2159-8290.CD-11-0206

APA

CBE

Birkbak NJ, Wang ZC, Kim J-Y, Eklund AC, Li Q, Tian R, Bowman-Colin C, Li Y, Greene-Colozzi A, Iglehart JD, Tung N, Ryan PD, Garber JE, Silver DP, Szallasi Z, Richardson AL. 2012. Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents. Cancer Drug Discovery and Development. 2(4):366-375. Available from: 10.1158/2159-8290.CD-11-0206

MLA

Vancouver

Author

Birkbak, Nicolai J.; Wang, Zhigang C.; Kim, Ji-Young; Eklund, Aron C.; Li, Qiyuan; Tian, Ruiyang; Bowman-Colin, Christian; Li, Yang; Greene-Colozzi, April; Iglehart, J. Dirk; Tung, Nadine; Ryan, Paula D.; Garber, Judy E.; Silver, Daniel P.; Szallasi, Zoltan; Richardson, Andrea L. / Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents.

In: Cancer Drug Discovery and Development, Vol. 2, No. 4, 2012, p. 366-375.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

Bibtex

@article{ece347c9a48c4f5eac71ec00abcf0072,
title = "Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents",
publisher = "Humana Press, Inc.",
author = "Birkbak, {Nicolai J.} and Wang, {Zhigang C.} and Ji-Young Kim and Eklund, {Aron C.} and Qiyuan Li and Ruiyang Tian and Christian Bowman-Colin and Yang Li and April Greene-Colozzi and Iglehart, {J. Dirk} and Nadine Tung and Ryan, {Paula D.} and Garber, {Judy E.} and Silver, {Daniel P.} and Zoltan Szallasi and Richardson, {Andrea L.}",
year = "2012",
doi = "10.1158/2159-8290.CD-11-0206",
volume = "2",
number = "4",
pages = "366--375",
journal = "Cancer Drug Discovery and Development",

}

RIS

TY - JOUR

T1 - Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents

A1 - Birkbak,Nicolai J.

A1 - Wang,Zhigang C.

A1 - Kim,Ji-Young

A1 - Eklund,Aron C.

A1 - Li,Qiyuan

A1 - Tian,Ruiyang

A1 - Bowman-Colin,Christian

A1 - Li,Yang

A1 - Greene-Colozzi,April

A1 - Iglehart,J. Dirk

A1 - Tung,Nadine

A1 - Ryan,Paula D.

A1 - Garber,Judy E.

A1 - Silver,Daniel P.

A1 - Szallasi,Zoltan

A1 - Richardson,Andrea L.

AU - Birkbak,Nicolai J.

AU - Wang,Zhigang C.

AU - Kim,Ji-Young

AU - Eklund,Aron C.

AU - Li,Qiyuan

AU - Tian,Ruiyang

AU - Bowman-Colin,Christian

AU - Li,Yang

AU - Greene-Colozzi,April

AU - Iglehart,J. Dirk

AU - Tung,Nadine

AU - Ryan,Paula D.

AU - Garber,Judy E.

AU - Silver,Daniel P.

AU - Szallasi,Zoltan

AU - Richardson,Andrea L.

PB - Humana Press, Inc.

PY - 2012

Y1 - 2012

N2 - DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of NtAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and NtAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation. Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair. SIGNIFICANCE: Mutations in BRCA genes cause defects in DNA repair that predict sensitivity to DNA damaging agents, including platinum; however, some patients without BRCA mutations also benefit from these agents. NtAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair. Cancer Discov; 2(4); 366–75. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 288

AB - DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of NtAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and NtAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation. Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair. SIGNIFICANCE: Mutations in BRCA genes cause defects in DNA repair that predict sensitivity to DNA damaging agents, including platinum; however, some patients without BRCA mutations also benefit from these agents. NtAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair. Cancer Discov; 2(4); 366–75. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 288

U2 - 10.1158/2159-8290.CD-11-0206

DO - 10.1158/2159-8290.CD-11-0206

JO - Cancer Drug Discovery and Development

JF - Cancer Drug Discovery and Development

IS - 4

VL - 2

SP - 366

EP - 375

ER -