Chromosome 12p Amplification in Triple-Negative/<i>BRCA1-</i>Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity.

ABSTRACT: Taxanes are the mainstay of treatment in triple-negative breast cancer (TNBC), with de novo and acquired resistance limiting patient's survival. To investigate the genetic basis of docetaxel resistance in TNBC, exome sequencing was performed on matched TNBC patient-derived xenografts (PDX) sensitive to docetaxel and their counterparts that developed resistance in vivo upon continuous drug exposure. Most mutations, small insertions/deletions, and copy number alterations detected in the initial TNBC human metastatic samples were maintained after serial passages in mice and emergence of resistance. We identified a chromosomal amplification of chr12p in a human BRCA1-mutated metastatic sample and the derived chemoresistant PDX, but not in the matched docetaxel-sensitive PD

SUBMITTER: Gomez-Miragaya J 

PROVIDER: S-EPMC7616973 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature