Tuesday, August 20 | 9 to 10 a.m. | Shelby 105

"Integrative Genomics Approaches for Unravelling the Polygenic Architecture of Triple Negative Breast Cancer"

Chindo Hicks, Ph.D.

Professor of Genetics and Bioinformatics

Director, Bioinformatics and Genomics Program

Department of Genetics

Louisiana State University Health Sciences Center

School of Medicine

Abstract: Triple-negative breast cancer (TNBC) is the most aggressive from of breast cancer. TNBC is characterized by aggressive clinical behavior, poor prognosis and poor clinical outcomes. It disproportionately impacts younger premenopausal women of African Ancestry. Currently there are no effective targeted therapies. Our understanding of TNBC and how best to treat it is hampered by the complexity of the human system in which it is manifested. Unlike simple Mendelian disorders, in which highly expressive, highly penetrant mutations make it possible to identify the causal genes, TNBC is a polygenetic disease originating from a more complex interplay between constellations of genetic (both germline and somatic variations) and epigenetic variation and a broad range of environmental factors such ethnicity and obesity.  These complex arrays of interacting factors are thought to affect entire molecular networks and signaling pathways driving TNBC. While Breast cancer-associated germline, somatic and epigenetic variants have been identified using high-throughput genotyping and next generation sequencing, the possible oncogenic interactions among them and their downstream molecular consequences remain unclear. To address this knowledge gap we have developed novel innovative unified approaches for unravelling the polygenetic architecture of TNBC. Key to our approach is integrating information on germline, somatic and epigenetic variation using gene expression as the intermediate phenotype. The key challenge that these approaches address is that of bridging precision oncology with precision prevention. Results from our studies thus far have shown that TNBC is an emergent property of functionally related genes interacting in complex gene regulatory networks and pathways enriched for germline, somatic and epigenetic variation. Results have further shown that these complex arrays of interacting genetic and epigenetic factors interact with modifying factors such as obesity to drive the disease and health disparities. Ongoing research includes integrating this information with information on socio-economic factors to map the molecular drivers of health disparities and to develop novel precision prevention strategies. 

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Meeting ID: 580 891 978