TFAP2B as a Regulator of Growth and Survival in Invasive Lobular Breast Cancer

Breast cancer impacts 1 in 8 women over their lifetime in the United States, and the death toll from breast cancer is expected to reach over 42,000 this year alone. Approximately 10-15% of invasive breast cancer are invasive lobular carcinoma (ILC) which are characterized by loss of E-Cadherin (CDH1), and expression of estrogen receptor (ER). ILC differs from invasive ductal carcinoma (IDC, ~80% of invasive breast cancer) with distinct clinical, pathological and molecular characteristics. Both ILC and IDC are treated the same way clinically, although ILC tumors have been shown to be less responsive to endocrine therapy with increased long-term recurrences 5-10 years after the original diagnosis. There is need to understand the distinct molecular, clinical and pathological differences of ILC compared to IDC and how these may be exploited for therapeutic benefit. An area that is specifically understudied are potential epigenetic differences between ER+ ILC and IDC, and how this affects the biology of disease. Advances in sequencing technologies and deeper exploration in underrepresented invasive lobular carcinoma samples has given researchers an opportunity to understand mechanism of genes and transcription factors in ILC. Publicly available sequencing data such as TCGA, METABRIC and internal cohorts allows researchers to explore queries and strengthen rationale through individual sequencing studies or pooled metadata analyses. I have investigated both public and house generated RNA sequencing data and methylation data, two in cell lines with alterations, either overexpressing CDH1 in ILC cell lines, or knocking out CDH1 expression in IDC cell lines, in-house data through sequencing a large panel of cell lines consisting of ILC, IDC, and ILC-like cell lines [4], as well as publicly available methylation data from TCGA in tumors and CCLE in cell lines. Exploring gene expression and pathway analysis suggests possibly therapeutic or prognostic pathways or genes effected uniquely in ILC. We found a transcription factor, part of the AP-2 family, TFAP2B that is hypomethylated in ILC, and is important for regulation of many genes. Members of this transcription factor family have shown to control expression of cancer related genes, such as ERα and CDH1 [1]