August 2019: Persi & Horn: the role of repetitive sequences in tumor evolution
Dr. Erez Persi and Prof. David Horn, and their colleagues, published a study in the journal PNAS where they presented evidence of another type of mutation active in cancer.
Cancer is primarily caused by mutations in genes. The most thoroughly studied cancer-associated mutations are single-letter substitutions in genes.
Dr. Erez Persi, (National Institutes of Health, a former Edmond J. Safra postdoc fellow), and Prof. David Horn, Edmond J. Safra member (Physics), and their colleagues, published a study in the journal PNAS where they presented evidence of another type of mutation active in cancer. These changes, collectively named “repeat instability”, are increases and/or decreases in repetitive segments of DNA and protein sequences.
The researchers developed a computational method to quantify variations in the repeat content of gene and protein sequences and used it to analyze sequence data from patients with a variety of cancers. They compared the sequences from the cancer tissue to those from healthy tissue adjacent to the cancer site, and relative to blood.
“This study shows that repetitive sequences, or DNA ‘hotspots,’ emerge early in tumor evolution but fade away in later phases, particularly during the transition to metastatic states, though they leave clear marks in the genome,” said Dr. Eugene Koonin, a co-author of the study and head of the Evolutionary Genomics Research Group at NIH’s National Library of Medicine. “Normal tissues adjacent to tumors show patterns of repetitive sequences that are similar to those detected in tumors, and therefore could be useful for early diagnosis of cancer,” Koonin added.
In addition to TAU and NIH researchers, researchers from University of Trento in Italy, and Weill Cornell Medicine in New York took part in the study.