Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

恢复 RAD51C 和 RAD51D 的继发性体细胞突变与高级别卵巢癌对 PARP 抑制剂 Rucaparib 的获得性耐药性有关

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作者:Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V Tinker, Nelson N H Teng, Maria I Harrell, Michael J Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M Kass, Meghan R Sullivan, Gregory J Brunette, Kara A Bernstein, Robert L Coleman, Anne Floquet, Michael Friedlander,

Significance

Analyses of primary and secondary mutations in RAD51C and RAD51D provide evidence for these primary mutations in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance. PARPi resistance due to secondary mutations underpins the need for early delivery of PARPi therapy and for combination strategies. Cancer Discov; 7(9); 984-98. ©2017 AACR.See related commentary by Domchek, p. 937See related article by Quigley et al., p. 999See related article by Goodall et al., p. 1006This article is highlighted in the In This Issue feature, p. 920.

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