Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies

J Exp Clin Cancer Res. 2022 Dec 14;41(1):343. doi: 10.1186/s13046-022-02554-4.

Abstract

Background: Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies.

Main body: Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin.

Short conclusion: The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.

Keywords: Patient-derived xenograft; Pre-clinical model; Thymoma.

Publication types

  • Letter

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Neoplasm Recurrence, Local / genetics
  • Neoplasms, Glandular and Epithelial*
  • Thymoma* / drug therapy
  • Thymoma* / genetics
  • Thymus Neoplasms* / drug therapy
  • Thymus Neoplasms* / genetics

Supplementary concepts

  • Thymic epithelial tumor