A cancer mystery more than 40 years old is solved thanks to epigenetics

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Before the primary oncogene mutations have been found in human cancer within the early 1980s, the 1970s supplied the primary information suggesting alterations within the genetic materials of tumors. In this context, the distinguished journal Nature revealed in 1975 the existence of a particular alteration within the reworked cell: an RNA chargeable for carrying an amino acid to construct proteins (switch RNA) was lacking a chunk, the enigmatic nucleotide ‘Y.’

After that excellent remark, nearly no developments have been made for forty-five years on the causes and penalties of not having the proper base in RNA.

In an article revealed in Proceedings of the National Academy of Sciences (PNAS) by the group of Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, ICREA Research Professor and Professor of Genetics on the University of Barcelona has solved this mystery by observing that in the protein that generates the Y is epigenetically inactivated, inflicting small however extremely 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 hypermodified guanine, but without connecting this characterization with its defect in tumor biology. 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,” explains Dr. Esteller in regards to the article in PNAS

Esteller provides, “Epigenetic blockade of the TYW2 gene occurs mainly in colon, stomach and uterine . And it has undesirable consequences for : 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.”

“In this regard, when we study patients with colon cancer in early stages, the epigenetic defect of TYW2 and the loss of the nucleotide Y is associated with those tumors that, although small in size, already lead to decreased survival of that person. 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,” concludes Esteller.


Researchers find epigenetic loss that changes how cells obtain energy from cancer


More data:
Margalida Rosselló-Tortella et al, Epigenetic lack of the switch RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.2003358117

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A cancer mystery more than 40 years old is solved thanks to epigenetics (2020, August 12)
retrieved 12 August 2020
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