A cancer mystery over 40 years old is solved thanks to epigenetics

Before the first oncogenic mutations were discovered in human cancer in the early 1980s, the 1970s yielded the first data suggesting changes in the genetic material of tumors. In this regard the prestigious magazine Nature published in 1975 the existence of a specific change in the transformed cell: an RNA responsible for carrying an amino acid to build proteins (RNA transfer) is missing a piece, the enigmatic nucleotide ‘Y.’

After that excellent observation, for forty-five years, virtually no developments were made about the causes and consequences of not having the right basis in RNA.

In an article published in Procedures of the National Academy of Sciences (PNAS) by the group of Drs. Manel Esteller, Director of the Josep Carreras Leukemia Research Institute, ICREA Research Professor and Professor of Genetics at the University of Barcelona has solved this mystery by observing that in cancer cells the nucleotide-producing protein Y is epigenetically inactive, making it small but highly aggressive. cause tumors.

“Since the original discovery in 1975, there has been a lot of biochemical work to characterize the enzymes involved in the various steps that lead to the desired nucleotide Y, a hypermodified guanine, but without this characterization. “We have built the bridge between these two worlds by showing that the epigenetic silence of the TYW2 gene is the cause of the loss of the elusive nucleotide Y,” explains Dr. Esteller about the article in PNAS

Esteller adds, “Epigenetic blockade of the TYW2 gene occurs mainly in cancerous, gastric and uterine cancers. And it has unusual consequences for healthy cells: the postman (RNA) that sends the signal to our body’s bricks ( proteins) to produce defects and the cell acquires a different appearance, far from the normal epithelium, which we call mesenchymal and which is associated with the appearance of metastasis. “

“As far as this is concerned, when we study patients with early-stage colon cancer, the epigenetic defect of TYW2 and the loss of the nucleotide Y are associated with those tumors which, although small in size, already lead to decreased survival of that person. “We now want to investigate how to restore the activity of the TYW2 gene and restore the necessary Y component to close the cycle of this story that began in 1975, at the end of modern molecular biology,” concludes Esteller.