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Birkbak NJ , Wang ZC , Kim JY , 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
Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents
Cancer Discov. 2012 Apr;2(4) :366-75
PMID: 22576213   
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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 (N(tAI)) 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 N(tAI) forecast a better initial response. We found an inverse relationship between BRCA1 expression and N(tAI) 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.
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 United States Cancer discovery Cancer Discov. 2012 Apr;2(4):366-75. Epub 2012 Mar 22.