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DNA Damage Predicts Drug Sensitivity in Breast Cancer

Accumulation of telomeric allelic imbalance predicts sensitivity to cisplatin

THURSDAY, March 22 (HealthDay News) -- Accumulation of telomeric allelic imbalance is indicative of defective DNA repair and predicts sensitivity to cisplatin treatment in some patients with breast and ovarian cancers, according to a study published online March 22 in Cancer Discovery.

Nicolai J. Birkbak, Ph.D., from the Technical University of Denmark in Lyngby, and colleagues examined whether there was an association between cisplatin sensitivity and genomic signatures indicative of defective DNA repair in cancer cell lines and tumors.

The researchers found that the number of regions with allelic imbalance extending to the telomere (NtAI) was associated with cisplatin sensitivity in vitro; and in patients with triple-negative breast cancer, NtAI predicted the pathological response to preoperative cisplatin treatment. Higher levels of NtAI predicted a better initial response in patients with serous ovarian cancer. In sporadic triple-negative breast cancer and serous ovarian cancers without BRCA1 or BRCA2 mutations, there was an inverse association between BRCA1 expression and NtAI.

"Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair," Birkbak and colleagues conclude.

Several authors disclosed a pending patent application based on this work; scientists from Affymetrix Inc. performed tumor genotyping under a research agreement with the company.

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