Abstract 4748: Revealing the molecular portrait of triple negative breast tumors from an understudied population through omics analysis of formalin-fixed and paraffin-embedded tissues

Abstract

Abstract Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal receptor 2 (HER2), is an aggressive form of breast cancer (BC) that is more prevalent in certain populations, in particular in low and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. We performed an integrative genomic analysis on FFPE samples from TNBC patients to identify molecular programs associated with this disease in an understudied population. We implemented whole exome sequencing of 12 tumor tissues and blood pairs, complemented with miRNA and mRNA profiling of the tumor tissues, using FFPE archived pathological samples from Mexican women. Sequencing analyses found TP53 and RB1 genes as the most frequently mutated. Transcriptional programs were characterized by the overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), the repression of cell cycle control pathways (TP53, RB1), the deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the utility of archival clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing the development of treatment strategies and of retrospective studies on the exploration of the geographic diversity of BC. Citation Format: Felipe Vaca-Paniagua, Rosa María Alvarez-Gomez, Carlos Perez-Plasencia, Hector Aquiles Maldonado-Martínez, Veronica Fragoso-Ontiveros, Federico Lasa-Gonsebatt, Luis Alonso Herrera, David Cantú, Enrique Bargallo-Rocha, Alejandro Mohar, Geoffroy Durand, Nathalie Forey, Catherine Voegele, Maxime Vallee, Florence Le Calvez-Kelm, James McKay, Maude Ardin, Stephanie Villar, Jiri Zavadil, Magali Olivier. Revealing the molecular portrait of triple negative breast tumors from an understudied population through omics analysis of formalin-fixed and paraffin-embedded tissues. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4748. doi:10.1158/1538-7445.AM2015-4748