A multi-gene expression signature in tumors is associated with aggressive disease and poor patient outcomes, and it has the potential to become a genetic cancer biomarker.

The human cell’s primary source of energy, the mitochondria plays an important role in the metabolism of cancer cells. In a study recently published in PLOS ONE, researchers from throughout the world, including Dario C. Altieri, M.D., president and chief executive officer, director of the Ellen and Ronald Caplan Cancer Center, and Robert and Penny Fox Distinguished Professor at The Wistar Institute, have identified a particular gene signature indicative of mitochondrial reprogramming in tumors that is associated with a poor patient outcome.

Scientists in Berlin have been studying a strange hereditary condition that causes half the people in certain families to have shockingly short fingers and abnormally high blood pressure for decades. If untreated, affected individuals often die of a stroke at the age of 50. Researchers at the Max Delbrück Center (MDC) in Berlin discovered the origin of the condition in 2015 and were able to verify it five years later using animal models: a mutation in the phosphodiesterase 3A gene (PDE3A) causes its encoded enzyme to become overactive, altering bone growth and causing blood vessel hyperplasia, resulting in high blood pressure.

“High blood pressure almost always leads to the heart becoming weaker,” says Dr. Enno Klußmann, head of the Anchored Signaling Lab at the Max Delbrück Center and a scientist at the German Centre for Cardiovascular Research (DZHK). As it has to pump against a higher pressure, Klußmann explains, the organ tries to strengthen its left ventricle. “But ultimately, this results in the thickening of the heart muscle – known as cardiac hypertrophy – which can lead to heart failure greatly decreasing its pumping capacity.”

Building on the CRISPR gene-editing system, MIT researchers have designed a new tool that can snip out faulty genes and replace them with new ones, in a safer and more efficient way.

Using this system, the researchers showed that they could deliver genes as long as 36,000 DNA base pairs to several types of human cells, as well as to liver cells in mice. The new technique, known as PASTE, could hold promise for treating diseases that are caused by defective genes with a large number of mutations, such as cystic fibrosis.

“It’s a new genetic way of potentially targeting these really hard to treat diseases,” says Omar Abudayyeh, a McGovern Fellow at MIT’s McGovern Institute for Brain Research. “We wanted to work toward what gene therapy was supposed to do at its original inception, which is to replace genes, not just correct individual mutations.”