Epigenetic Profiling Of Tumor Metastases May Improve Therapeutic Options

Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with:
Eric Jonasch, MD
Associate Professor Department of Genitourinary Medical Oncology
University of Texas MD Anderson Cancer Center
Houston, TX

and

Dr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale ArizonaDr. Thai H. Ho, MD Ph.D.
Department of Oncology
Mayo Clinic Scottsdale Arizona

Medical Research: What is the background for this study? What are the main findings?

Response: The blueprints of a cell are encoded in DNA strands (its genome) which are highly compressed in order to fit into a tiny cell. The reading (called the epigenome) of these DNA ‘blueprints’ determines whether that cell will develop into a kidney cell or another type of cell. However, in cancer, errors occur either in the blueprints themselves or the cell makes mistakes in reading the blueprints. Cancers of the kidney affect more than 61,000 patients annually and over 13,000 patients die annually, making it one of the top 10 leading causes of cancer deaths. Studies have revealed that mutations occur in genes that regulate how our DNA ‘blueprints’ are compacted in greater than >50% of kidney cancers, making these genes as a group the most frequently mutated. In our study, we identified that these errors that initially arise in an early kidney cancer lead to propagation of these same errors in metastases, a phenomenon in which the cancer has spread to another organ and is a major cause of death. Furthermore, we generated a detailed map of these epigenomic changes in patient-derived tumors.

Medical Research: What should clinicians and patients take away from your report?

Response:  Standard treatments in kidney cancer rarely produce a durable response and most studies focus on the primary tumor. Expanding the epigenomic profiling to patient derived tissue metastases may improve upon therapeutic selection and is currently being offered as part of a research protocol at Mayo Clinic.

http://newsnetwork.mayoclinic.org/discussion/beating-advanced-cancers-new-epigenomic-block-for-cancer-progression/

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Future research studies could use kidney cancer as a paradigm for identifying vulnerabilities in metastases, a major cause of mortality, and alter the course of other tumors with similar errors.

Citation:

High-resolution profiling of histone h3 lysine 36 trimethylation in metastatic renal cell carcinoma

T H Ho1,2,17, I Y Park3,17, H Zhao4, P Tong4, M D Champion2,5, H Yan2,6, F A Monzon7,18, A Hoang8, P Tamboli9, A S Parker10, R W Joseph11, W Qiao12, K Dykema13, N M Tannir8, E P Castle14, R Nunez-Nateras14, B T Teh13, J Wang4, C L Walker3, M-C Hung and E Jonasch

Oncogene advance online publication 15 June 2015; doi: 10.1038/onc.2015.221

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