WCRC-25: A novel luminal Invasive Lobular Carcinoma cell line model

Breast cancer is categorized by the molecular and histologic presentation of the tumor; with the major histologic subtypes observed in patients being No Special Type (NST; commonly known as Invasive Ductal Carcinoma, IDC) and Invasive Lobular Carcinoma (ILC). ILC are characterized by growth in a single file discohesive manner with stromal infiltration attributed to their hallmark loss of E-cadherin (CDH1). The Cancer Cell Line Encyclopedia (CCLE) currently only lists three ILC cell lines; emphasizing the need to expand the inventory of models available to researchers. Here we report the successful establishment and characterization of a novel ILC cell line, WCRC-25, from a metastatic pleural effusion from a postmenopausal Caucasian woman with metastatic ILC. WCRC-25 is an ER-negative luminal epithelial ILC cell line with both luminal and Her2-like features. It exhibits anchorage independent growth and haptotactic migration towards Collagen I. Sequencing revealed a CDH1 Q706* truncating mutation in WCRC-25, together with mutations in FOXA1, CTCF, BRCA2 and TP53 which were also seen in a series of metastatic lesions from the patient. Copy number analyses revealed amplification and deletion of genes frequently altered in ILC while optical gene mapping (Bionano) revealed novel structural rearrangements. RNA-seq analysis comparing the primary tumor, metastases and the cell line revealed signatures for cell cycle progression and receptor tyrosine kinase signaling. To assess targetability, we treated WCRC-25 with AZD5363 and Alpelisib confirming WCRC-25 as susceptible to PI3K/Akt signaling inhibition as predicted by our RNA sequencing analysis. In conclusion, we report WCRC-25 as a novel ILC cell line with much promise as a valuable research tool to advance our understanding of ILC and its therapeutic vulnerabilities. Overall design: RNA sequencing analysis of multifocal metastases from the same patient and patient-derived cell line models.