Researchers at the University of Maryland and the National Cancer Institute have identified 12 distinct types of gene-pair interactions in which varying levels of expression in the 2 genes correlated with the survival of patients with cancer. The results suggest that genes involved in such paired interactions could provide new targets for cancer therapy, according to the study authors.
 
"Relying on specific cancer vulnerabilities, such as a particular mutated gene's functional relationship with other genes, is potentially an effective approach to treating cancer," said senior author Sridhar Hannenhalli, PhD.
 
This approach was previously explored in a gene-pair relationship called synthetic lethality, in which inactivation of both genes is lethal to a cell, but inactivation of 1 gene is not. For cancer cells in which mutations inactivate 1 gene, drugs that inhibit the partner gene would be lethal to cancer cells but have minimal to no effect on healthy tissue in which the first gene is expressed normally, according to the authors.
 
The new study revealed a greater number of varying gene-pair relationships than synthetic lethality, indicating to researchers that the relationships may offer more potential targets for cancer therapy.
 
Using data from 5288 tumors representing 18 different cancer types, the research team defined 6 interactions in which each gene in a pair could be expressed at a low, medium, or high level. They then considered that each of those combinations could be associated with a positive or negative outcome for patient survival. The total number of potential gene-pair relationship types was 12.
 
The researchers then used a novel computational strategy to assess all possible combinations of genes in their dataset. Out of 163 million potential gene pairs, the researchers identified nearly 72,000 gene-pair interactions associated with positive or negative patient survival. Of the genes involved in these interactions, a significant proportion are known to be involved in cell division and proliferation, which have clear links to cancer.
 
According to the study authors, identifying gene-pair relationships can help scientists understand why mutations in certain genes lead to cancer in 1 tissue but not another, because their interacting partners might be expressed differently in different types of tissue.
 
Similarly, gene-pair relationships could explain why certain drugs are effective for some patients but not others. The relationships also might help researchers identify subtypes of certain cancers, such as breast cancer, which may help with prognosis and therapy, the study concluded.
 
References
  1. Scientists Identify New Genetic Interactions That May Impact Cancer Outcome [news release]. University of Maryland website. Published July 23, 2019. https://cmns.umd.edu/news-events/features/4464. Accessed August 1, 2019.