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Carcinogenesis is just another form of speciation, proposes new theory

June 11, 2017

"If humans changed their karyotype - the number and arrangement of chromosomes - we would either die or be unable to mate, or in very rare cases become another species," Duesberg said. But cancer cells just divide and make more of themselves. They don't have to worry about reproduction, which is sensitive to chromosomal balance. In fact, as long as the genes for mitosis are still intact, a cancer cell can survive with many disrupted and unbalanced chromosomes, such as those found in an aneuploid cell, he said.

The karyotype does change as a cancer cell divides, because the chromosomes are disrupted and thus don't copy perfectly. But the karyotype is "only flexible within a certain margin," Duesberg said. "Within these margins it remains stable, despite its flexibility."

Karyographs display karyotype variability

Duesberg and his colleagues developed karyographs as a way to display the aneuploid nature of a cell's karyotype and its stability across numerous cell cultures. Using these karyographs, he and his colleagues analyzed several cancers, clearly demonstrating that the karyotype is amazingly similar in all cells of a specific cancer line, yet totally different from the karyotypes of other cancers and even the same type of cancer from a different patient.

HeLa cells are a perfect example. Perhaps the most famous cancer cell line in history, HeLa cells were obtained in 1951 from a cervical cancer that eventually killed a young black woman named Henrietta Lacks. The 60-year-old cell line derived from her cancer has a relatively stable karyotype that keeps it alive through division after division.

"Once a cell has crossed that barrier of autonomy, it's a new species," Duesberg said. "HeLa cells have evolved in the laboratory and are now even more stable than they probably were when they first arose."

The individualized karyotypes of cancers resemble the distinct karyotypes of different species,, Duesberg said. While biologists have not characterized the karyotypes of most species, no two species are known that have the same number and arrangement of chromosomes, including those of, for example, gorillas and humans, who share 99 percent of their genes.

Duesberg argues that his speciation theory explains cancer's autonomy, immortality and flexible, but relatively stable, karyotype. It also explains the long latency period between initial aneuploidization and full blown cancer, because there is such a low probability of evolving an autonomous karyotype.

"You start with a chromosomal mutation, that is, aneuploidy perhaps from X-rays or cigarettes or radiation, that destabilizes and eventually changes your karyotype or renders it non-viable," he said. "The rare viable aneuploidies of cancers are, in effect, the karyotypes of new species."

Duesberg hopes that the carcinogenesis-equals-speciation theory will spur new approaches to diagnosing and treating cancer. Vincent, for example, suspects that cancers are operating right at the edge of survivability, maintaining genomic flexibility while retaining the ability to divide forever. Driving them to evolve even faster, he said, "might push them over the edge."

Source: University of California - Berkeley