Cancer cells with extra chromosomes depend on those chromosomes for tumor growth
A new Yale study reveals that cancer cells with additional chromosomes rely on them for tumor growth. Eliminating these extra chromosomes prevents the cells from forming tumors. The findings suggest that selectively targeting extra chromosomes may offer a new route for treating cancer.
The study was published on July 6 in the journal Science.
Human cells typically have 23 pairs of chromosomes; extra chromosomes are an anomaly known as aneuploidy.
If you look at normal skin or normal lung tissue, for example, 99.9% of the cells will have the right number of chromosomes. But we've known for over 100 years that nearly all cancers are aneuploid.
Jason Sheltzer, assistant professor of surgery at Yale School of Medicine and senior author of the study
However, it was unclear what role extra chromosomes played in cancer - for instance, whether they cause cancer or are caused by it.
"For a long time, we could observe aneuploidy but not manipulate it. We just didn't have the right tools," said Sheltzer, who is also a researcher at Yale Cancer Center. "But in this study, we used the gene-engineering technique CRISPR to develop a new approach to eliminate entire chromosomes from cancer cells, which is an important technical advance. Being able to manipulate aneuploid chromosomes in this way will lead to a greater understanding of how they function."
The study was co-led by former lab members Vishruth Girish, now an M.D.-Ph.D. student at Johns Hopkins School of Medicine, and Asad Lakhani, now a postdoctoral researcher at Cold Spring Harbor Laboratory.
Using their newly developed approach - which they dubbed Restoring Disomy in Aneuploid cells using CRISPR Targeting, or ReDACT - the researchers targeted aneuploidy in melanoma, gastric cancer, and ovarian cell lines. Specifically, they removed an aberrant third copy of the long portion - also known as the "q arm" - of chromosome 1, which is found in several types of cancer, is linked to disease progression, and occurs early in cancer development.
"When we eliminated aneuploidy from the genomes of these cancer cells, it compromised the malignant potential of those cells and they lost their ability to form tumors," said Sheltzer.
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