Establishment and characterization of a novel breast implant-associated anaplastic large cell lymphoma cell line and PDX model (BIA-XR1) with a unique KRAS mutation

Ioanna Xagoraris; Konstantina Stathopoulou; Roberta D' Aulerio; Minghui He; Anett Ketscher; Kenbugul Jatta; Felix Haglund de Flon; Gisela Barbany; Richard Rosenquist; Lisa S Westerberg; George Z Rassidakis

doi:10.1016/j.retram.2023.103401

Establishment and characterization of a novel breast implant-associated anaplastic large cell lymphoma cell line and PDX model (BIA-XR1) with a unique KRAS mutation

Curr Res Transl Med. 2023 Jul-Sep;71(3):103401. doi: 10.1016/j.retram.2023.103401. Epub 2023 Jun 20.

Affiliations

¹ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
² Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
³ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
⁵ Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
⁶ Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden. Electronic address: georgios.rassidakis@ki.se.

PMID: 37364351
DOI: 10.1016/j.retram.2023.103401

Abstract

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma type with distinct clinical, molecular and genetic features. Establishment of BIA-ALCL cell lines and patient-derived xenograft (PDX) models are essential experimental tools to investigate the molecular pathogenesis of the disease. We characterized a novel BIA-ALCL cell line and PDX model, named BIA-XR1, derived from a patient with textured breast implant who developed lymphoma. Next-generation sequencing revealed a STAT3 mutation, commonly detected in BIA-ALCL, and a unique KRAS mutation reported for the first time in this lymphoma type. Both JAK/STAT3 and RAS/MEK/ERK oncogenic pathways were activated in BIA-XR1, which are targetable with clinically available agents.

Keywords: Breast implant-associated anaplastic large cell lymphoma; Cell line; Patient-derived xenograft.