Q: What is the focus of your research in Dr. Cairns’ lab?
A: Ibragimova: During my postdoc training with Dr. Cairns, I studied the global promoter methylome of the cancer cell. One of the projects focused on the biologically heterogeneous group of small renal masses, the most common presentation of renal cancer. By implementing advanced technologies in DNA methylation, I identified a unique methylation signature for each of three histological subtypes of renal cell cancer and a benign renal tumor, oncocytoma. I am also using next-generation sequence technology in a subset of women with ductal carcinoma in-situ (DCIS) who later developed invasive breast cancer to determine whether sequence mutations are already present in the precursor DCIS lesions.
Q: What is most important about Dr. Ibragimova’s research?
A: Cairns: Small renal masses (SRMs) have a different biology and behavior. Patients with SRMs are candidates for active surveillance where differential diagnoses of more aggressive histology subtypes such as clear cell cancers, or molecular subtypes such as methylator phenotype-RCC as candidates for epigenetic therapy, could inform clinical management. Ilsiya is designing and testing a panel of methylated genes for differential diagnosis of SRMs in blood or urine from patients who have not had a needle biopsy.
She is also investigating whether methylation of particular genes and sequence mutation in other genes in DCIS can identify women at high risk of subsequent invasive breast cancer. Hybrid signatures of different types of mutation will offer the most accurate information about a patient’s cancer.
Q: What are the implications of your research for patients?
A: Ibragimova: Distinguishing subtypes of small renal masses is of clinical importance because they have different prognoses and therefore different management schemes. I hope my research will lead to identification of biomarkers, including for noninvasive approaches, which will allow us to identify patient populations that can be successfully managed by active surveillance instead of surgical intervention. The successful completion of the DCIS project could lead to a strategy to identify women at higher risk of progression who could receive preventive therapy, increased screening, and, hopefully, earlier detection.
Q: In what direction should this research go over the next decade?
A: Ibragimova: As our knowledge of genetics and epigenetics evolves, it is becoming clear that they are inextricably connected. The recent genome sequencing of kidney cancer DNA revealed rare mutations in the genes of chromatin/epigenetic modifiers. We will need to clarify the real contribution of epigenetic alterations to a wide range of diseases, and in particular, the interplay among epigenetics, the environment, and aging.
Q: How will patients benefit from research conducted by Dr. Ibragimova and others in your lab?
A: Cairns: Precision medicine will incorporate epigenomic alterations into decision-making for current cytotoxic and/or small molecule protein inhibitor chemotherapies, as well as for epigenetic drug therapies. Epigenetic changes may precede genetic changes in the development of some cancers, with important implications for risk assessment and preventive therapy. Using blood and other body fluids as a “liquid biopsy” are compelling alternatives to traditional, potentially invasive biopsy for epigenetic or genetic profiling and for monitoring efficacy of therapy and dynamic clonal changes in the tumor.