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40-Year-Old Cancer Mystery Solved Thanks to Epigenetics

The mystery was discovered and had remained unsolved since the dawn of modern molecular biology.

The first-ever data to suggest the occurrence of alterations in the genetic material of tumors was discovered in the 70s, followed by the discovery of the first oncogene mutations in human cancer cells in the early 80s. 

In 1975 specifically, scientific journal Nature published an article detailing a specific alteration in the transformed cell: an RNA responsible for carrying an amino acid to build proteins (transfer RNA) had a piece missing, which was dubbed the enigmatic nucleotide "Y".

Now, thanks to a newly-published study by a University of Barcelona Professor of Genetics, this mystery has finally been solved.

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In an article published in Proceedings of the National Academy of Sciences (PNAS), a group of researchers led by Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, ICREA Research Professor and Professor of Genetics at the University of Barcelona, detailed how they solved the mystery by describing the fact that the protein that generates the nucleotide "Y" in cancer cells is epigenetically inactivated, causing small but highly aggressive tumors.

"Since the original discovery in 1975, there has been much biochemical work to characterize the enzymes involved in the different steps that lead to the desired nucleotide Y, a hyper modified guanine, but without connecting this characterization with its defect in tumor biology," Dr. Esteller explained in a press release.

"We have built the bridge between these two worlds by demonstrating that the epigenetic silencing of the TYW2 gene is the cause of the loss of the elusive nucleotide Y," Dr. Esteller continued.

Esteller also explained how the Epigenetic blockade of the TYW2 gene occurs in the stomach, colon, and uterine cancer. This has terrible consequences for healthy cells in a human. Essentially, "the postman (RNA) that sends the signal to produce the bricks of our body (proteins) begins to accumulate errors and the cell takes on a different appearance, far from the normal epithelium, which we call mesenchymal and which it is associated with the appearance of metastasis," Esteller said.

What's the next step for the researchers? "We would like to explore now how to restore the activity of the TYW2 gene and restore the necessary Y component in order to close the cycle of this story that began so brilliantly in 1975, at the dawn of modern molecular biology," explains Esteller. What a remarkable achievement in the field of cancer research that would be.

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