26 May Breast and Ovarian Cancers May Have Common Epigenetic Origin
MedicalResearch.com Interview with:
Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism.
MedicalResearch.com: What should readers take away from your report?
Dr. Sarkar: The take home message from this study is that breast and ovarian cancer may have an epigenetic origin. The origin means the formation of cancer progenitor cells. Usually, cancer progression is a slow process. Once the cancer progenitor cells are formed, they may progress quickly. Traditional therapies don’t kill both cancer progenitor cells and drug resistant cancer cells, leading to relapse, which is very common. A combination therapy including epigenetic drug should reduce cancer relapse.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Sarkar: One of the most important questions which remains to be solved is how cancer progenitor cells form. Many hypotheses are out there including the sequestering of gradual mutations. Heterogeneity in tumors harboring many different types of mutations makes it very difficult to pin point the actual causes of tumor development. It may appear that this process is completely disorganized and random, but other studies showed that even very heterogeneous tumors may originate from just a few cancer stem/progenitor cells. We believe that these progenitor cells arise from predisposed cells, and are formed by a well-organized epigenetic mechanism in terms of DNA methylation and histone modifications. This mechanism should be an aberration of epigenetic process, which is well-orchestrated during embryogenesis and development. Further progression and heterogeneous development of tumors depends on type of mutations they acquire and other genetic abnormalities present, inherited or acquired. Finding this epigenetic imbalance, which may be similar or somewhat different for many types of cancers is the key to understanding cancer progression and development.
MedicalResearch.com: Is there anything else you would like to add?
Dr. Sarkar: Regulation of tissue specific gene expression by epigenetic mechanism, which shows fidelity in all mammal tissue/organ development suggest that aberration of this process is not only an important event to initiate cancer as discussed above but also possibly involved in other disease/disorder processes depending on how , where and when it happens.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Mckenna Longacre, Nicole Snyder, Genevieve Housman, Meghan Leary, Karolina Lapinska, Sarah Heerboth, Amber Willbanks, Sibaji Sarkar. A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis. International Journal of Molecular Sciences, 2016; 17 (5): 759 DOI:10.3390/ijms17050759
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