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Addressing the Elephant in the Room in Cancer Genetic

“People always knew cancer chromosomes were a big mess, but they didn't know how much of this mess was important,” Elledge said.

The findings also suggest that the “Two-Hit” hypothesis, a central view on tumor suppression proposed by the geneticist Alfred G. Knudson, might have been generalized to make sporadic cancers appear simpler than they actually are.

According to the “Two-Hit” model, the first hit is not enough to contribute to the formation of a tumor in familial cancers, but mutations to the second copy of the same chromosome were thought to provide the second hit that drives the development of tumors.

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In the study, scientists suggest that most tumor suppressor genes may be haploinsufficient  in sporadic cancers, meaning that one copy of the gene is not fully functional anyway. If that is the case, the second hit might not be necessary to cause tumor development.

Elledge added that the next step is to engineer deletion and amplifications to recreate the events that occur in cancer cells.

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