Heteroplasmy as a biomarker and therapeutic target in cancer

13^th Asia-Pacific Oncologists Annual Meeting

October 17-19, 2016 Kuala Lumpur, Malaysia

Ravi Sachidanandam

Icahn School of Medicine at Mount Sinai, USA

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

It is increasingly appreciated that heteroplasmy, the occurrence of multiple mtDNA haplotypes in a cell, plays an important biological role, but its features are not well understood. Accurately determining the diversity of mtDNA has been difficult, due to the relatively small amount of mtDNA in each cell (<1% of the total DNA), the intercellular variability of mtDNA content and mtDNA pseudogenes (Numts) in nDNA. To understand the nature of heteroplasmy, we developed Mseek, a novel technique to purify and sequence mtDNA. Mseek yields high purity (>90%) mtDNA and its ability to detect rare variants is limited only by sequencing depth, providing unprecedented sensitivity and specificity. Using Mseek, we have established that heteroplasmy is ubiquitous and stable, through experiments in cell lines and several human samples. We have determined that heteroplasmy is maintained at the level of the single cell. Applying Mseek to several normal-tumor samples from breast cancer patients, we have demonstrated that selection of specific haplotypes occurs in tumors, compared to the normal cells. The restriction of haplotype diversity arises through selection at the level of mtDNA, since cellular selection cannot steer mtDNA haplotypes. The haplotypes provide a biomarker that is easy to monitor for the effects of treatments by monitoring the mtDNA released by dying cells. We are developing methods of targeting selected mtDNA haplotypes, as a therapeutic intervention in cancer.

Biography :

Email: ravi.mssm@gmail.com