Genomic profile of metastatic breast cancer patient-derived xenografts established using percutaneous biopsy

Seongyeong Kim, Dongjin Shin, Ahrum Min, Minjung Kim, Deukchae Na, Han Byeol Lee, Han Suk Ryu, Yaewon Yang, Go Un Woo, Kyung Hun Lee, Dae Won Lee, Tae Yong Kim, Charles Lee, Seock Ah Im, Jong Il Kim

Research output: Contribution to journalArticlepeer-review


Background: Metastatic breast cancer (mBC) is a complex and life-threatening disease and although it is difficult to cure, patients can benefit from sequential anticancer treatment, including endocrine therapy, targeted therapy and cytotoxic chemotherapy. The patient-derived xenograft (PDX) model is suggested as a practical tool to predict the clinical outcome of this disease as well as to screen novel drugs. This study aimed to establish PDX models in Korean patients and analyze their genomic profiles and utility for translational research. Methods: Percutaneous core needle biopsy or punch biopsy samples were used for xenotransplantation. Whole exome sequencing and transcriptome analysis were performed to assess the genomic and RNA expression profiles, respectively. Copy number variation and mutational burden were analyzed and compared with other metastatic breast cancer genomic results. Mutational signatures were also analyzed. The antitumor effect of an ATR inhibitor was tested in the relevant PDX model. Results: Of the 151 cases studied, 40 (26%) PDX models were established. Notably, the take rate of all subtypes, including the hormone receptor-positive (HR +) subtype, exceeded 20%. The PDX model had genomic fidelity and copy number variation that represented the pattern of its donor sample. TP53, PIK3CA, ESR1, and GATA3 mutations were frequently found in our samples, with TP53 being the most frequently mutated, and the somatic mutations in these genes strengthened their frequency in the PDX model. The ESR1 mutation, CCND1 amplification, and the APOBEC signature were significant features in our HR + HER2- PDX model. Fulvestrant in combination with palbociclib showed a partial response to the relevant patient’s tumor harboring the ESR1 mutation, and CCND1 amplification was found in the PDX model. AZD6738, an ATR inhibitor, delayed tumor growth in a relevant PDX model. Conclusions: Our PDX model was established using core needle biopsy samples from primary and metastatic tissues. Genomic profiles of the samples reflected their original tissue characteristics and could be used for the interpretation of clinical outcomes.

Original languageEnglish
Article number7
JournalJournal of Translational Medicine
Issue number1
StatePublished - Dec 2021


  • Metastatic breast cancer
  • Patient-derived xenograft
  • Whole-exome sequencing


Dive into the research topics of 'Genomic profile of metastatic breast cancer patient-derived xenografts established using percutaneous biopsy'. Together they form a unique fingerprint.

Cite this