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Predisposition to cancer and cancer progression can result from gene mutations that cause elevated rates of genetic damage. Similarly, carcinogens, including some that are used in chemotherapy during cancer treatment, act by damaging the DNA. A new study from Roswell Park Cancer Institute offers insights into the mechanisms that can lead to genetic mutations and proposes opportunities for developing prognostic tests for specific blood disorders and blood cancers based on these striking findings. The study has been published online ahead of print in the journal PLOS Genetics.

For this study, Steven Pruitt PhD Professor of Oncology in the Department of Molecular and Cellular Biology at Roswell Park, led a team of scientists that conducted next-generation sequencing of red blood cell micronuclei (Mic-Seq) to define the locations of chromosome breaks genome-wide. Traditional micronucleus assays have been used to show increases in DNA damage by measuring the frequency of micronuclei, but failed to reveal the locations of the damage. In contrast, Mic-Seq reveals where damage is occurring and identifies the genes that are likely to become compromised, adding new insights into how the gene mutations that can lead to cancer progression arise.

“These studies suggest that Mic-Seq can provide an effective means for identifying and predicting locations that are susceptible to genetic damage in a variety of circumstances and these predictions may have prognostic value,” says Dr. Pruitt. “We plan additional studies extending this Mic-Seq approach where we hope to develop personalized prognostic tests to identify patients who are at risk of progression of myelodysplastic syndrome to acute myeloid leukemia or are likely to suffer therapy-related secondary leukemia following treatment for childhood cancer.”

This research was supported, in part, by grants from R01CA130995 and R01AGO41854. The study, “A Signature of Genomic Instability Resulting from Deficient Replication Licensing,” is available at journals.plos.org.

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The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.

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