Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors

• Published in: PLoS ONE 2016, Vol.11 (4)
• Main Authors: Norton, Nadine, Advani, Pooja P, Serie, Daniel J, Geiger, Xochiquetzal J, Necela, Brian M, Axenfeld, Bianca C, Kachergus, Jennifer M, Feathers, Ryan W, Carr, Jennifer M, Crook, Julia E, Moreno-Aspitia, Alvaro, Anastasiadis, Panos Z, Perez, Edith A, Thompson, E. Aubrey
• Format: Report
• Language: English
• Subjects: Analysis; Breast cancer; Care and treatment; Gene expression; Genetic aspects; Genetic variation; Physiological aspects; Risk factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153411

Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC. We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual. 35 and 34 genes were upregulated (FC>2) and down-regulated (FC