14 DAY TRIAL // British and American researchers found a new clue that explains the way that cancers appear sometimes, without any warning.
Most cancers evolve by following certain steps – cells become premalignant, then abnormally large before turning into cancerous cells, and if early detected, treatments can prove effective, but what's the explanation behind those cancers that appear from nowhere?
The researchers analyzed DNA sequences of many cancer samples of various types, and concluded that sudden cancers can appear as a consequence of one-off cellular crises, that involve tens to hundreds of genomic rearrangements.
The study started to analyze the patterns of DNA rearrangements in cancers in general, which revealed cases of massive rearrangements in very limited areas of the genome, involving one or a few chromosomes.
Peter Campbell, of Wellcome trust Sanger Institute and the University of Cambridge, said that they tried to come up with a scenario replacing certain events that could have led to such a wide rearrangement, but that “was impossible to do.”
Instead, they concluded that the chromosomes had been broken in a single event, and then patched back together, “in higgledy piggledy fashion.”
Campbell explained that “the cell should say, 'That's it,' and give up but instead it tries to piece the chromosomes back together like a valuable piece of porcelain.
“They attempt to reconstruct the un-reconstructable and they wind up with a disastrous genome that shortens the road to cancer.
“We think this process happens as a part of life to produce chromosomal damage on a spectacular scale,” added Campbell.
“Probably almost always the cell dies, but sometimes the cell tries to rescue itself.
“It repairs itself incorrectly and a genome emerges with incredible cancerous potential.”
According to researchers' data, this chromosome shattering phenomenon, called chromothripsis, appears in 2% - 3% of all cancers, and in 25% of bone cancers (quite significant).
The scientists said that the causes of such large rearrangements are not fully understood yet, but single pulses of ionizing radiation could play a role.
Campbell explained that ionizing radiation is known to cause double stranded DNA breaks that could generate breaks involving a part of or the entire chromosome.
The researchers' next step is to look at cancers in people that are known to have been exposed to ionizing radiation, and gather any evidence of these sorts of rearrangement.
“If we can understand its roots, then we may learn how to prevent that kind of damage from happening,” said Campbell.
“Whatever the mechanism of damage, the consequences are profound," the researchers write in conclusion.
“Faced with hundreds of DNA breaks, the cell's DNA repair machinery attempts to rescue the genome.
“The resultant hodgepodge bears little resemblance to its original structure, and the genomic disruption has wholesale and potentially oncogenic effects.”
The findings were reported in the January 7th issue of the journal Cell, a Cell Press publication.