Although global deaths caused by different types of cancer have been declining, managing this devastating disease
remains challenging, particularly in our country Georgia, which is situated, approximately 1448 km from the site of the
Chernobyl nuclear power plant accident, which occurred in 1986. Food products and manufactured goods were shared
and distributed among those 15 republics including Georgia. All these factors contributed to the exposure of Georgians
to low-dose radiation. A decade after the Chernobyl nuclear power plant accident, an increased incidence of
hematological malignancies, including multiple myeloma (MM) was observed among people residing in the
contaminated region.
While the effects of radiation on DNA are widely studied, radiation can also damage RNA through alteration of RNA
processing mechanisms. Our long-term interest includes, but is not limited to, understanding the broad effects of lowdose radiation on transcriptome changes through epigenetic mechanisms, including its effects on RNA splicing and its
regulation. To achieve our goals, we will explore the effects of low doses of radiation on RNA splicing in GE Pts
(Georgian patients with hematological malignancies multiple myeloma (MM)) for the following reasons: (1) an increased
incidence of MM has been reported in the region affected by the Chernobyl accident; (2) our ongoing studies that monitor
alterations in the transcriptome of patients with MM showed a significant impact of splicing alterations on the overall
clinical outcome for these patients; and (3) the fundamental role of RNA splicing in human biology and its relevance in
cancer are among the most unexpected and dramatic findings that have arisen from the cancer genome sequencing
project. The hypothesis of this application is that Georgian MM patients (GE Pts) exposed to the Chernobyl accident
may have acquired transcriptome changes through epigenetic alterations, with particular emphasis on altered
RNA splicing.
To test my hypothesis: (1) we will determine the RNA splicing signature in GE MM Pts and (2) identify the cause
of altered splicing in these patients. In taking these approaches our studies will identify selective genetic alterations in
GE MM Pts and will lead to the identification of novel biomarkers and drug targets, consequently providing unique
therapeutic possibilities for these patients.