Breast Cancer Brain Metastasis: Genomic and Epigenomic Analysis

Bodour Salhia, PhD Assistant Professor Integrated Cancer Genomics Division Translational Genomics Research Institute Phoenix, Arizona, 85004MedicalResearch.com Interview with:
Bodour Salhia, PhD
Assistant Professor
Integrated Cancer Genomics Division
Translational Genomics Research Institute
Phoenix, Arizona, 85004

MedicalResearch.com: What are the main findings of the study?

Dr. Salhia: Our study identified novel rare genomic and epigenomic events underlying breast cancer metastasis to brain. We demonstrated that we could molecularly subtype breast cancer brain metastasis the same way we can subtype primary breast cancer. From this analysis we found that the Luminal B subtype was the most common subtype in our cohort, followed by Her2+/ER- enriched tumors and Basal-like tumors. Each of these subtypes displayed genetic and epigenetic features reminiscent of primary breast cancer. We demonstrated that these tumors have a strong predilection to grow by activating pathways involved in G2/M cell cycle progression, whereas, many genes involved in cell migration were epigenetically silenced. Broad amplification of chromosome 8q was common, which resulted in the upregulation of important genes.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Salhia: Certainly, gain of 8q has been previously described for breast cancer and has been associated with disease progression and poor patient prognosis. What was surprising to us was the amplification of the cMYC oncogene on 8q without concomitant expression. If we assume that the 8q locus is important in the development of brain metastasis, this data suggests that other genes on 8q (not cMYC) may be driving metastasis to brain.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Salhia: This is an important study that integrated multiple genomic datasets to determine underlying molecular characteristics of brain metastasis. Survival with brain metastasis remains quite poor. So we want patients to walk away with a sense of hope, as we get closer to finding better ways to treat this disease.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Salhia: Breast cancer brain metastasis is a really significant problem and a huge unmet need. We now want to dig deeper and uncover more specific genomic links and study new ways to treat these patients so we can dramatically improve outcomes.

 

Citation:

Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

Bodour Salhia, Jeff Kiefer, Julianna T. D. Ross, Raghu Metapally, Rae Anne Martinez, Kyle N. Johnson, Danielle M. DiPerna, Kimberly M. Paquette, Sungwon Jung, Sara Nasser, Garrick Wallstrom, Waibhav Tembe, Angela Baker, John Carpten, Jim Resau, Timothy Ryken, Zita Sibenaller, Emanuel F. Petricoin, Lance A. Liotta, Ramesh K. Ramanathan, Michael E. Berens, Nhan L. Tran Research Article | published 29 Jan 2014 | PLOS ONE

 

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