What causes cancer? Science and medicine have been trying to answer this question for centuries. In the late 1800s, scientists observed that most tumors have an odd number of chromosomes. They thought this imbalance, called aneuploidy, may be a driving force in cancer development. Since then, technological advancements鈥攁nd limitations鈥攈ave pushed science in other directions. But now, thanks to experiments performed at 黑料吃瓜资源, cancer research could come full circle.
Asad Lakhani guides a tour of his aneuploidy research at CSHL.
The experiments were led by Asad Lakhani, who recently graduated from the CSHL School of Biological Sciences, his doctoral advisor, Jason Sheltzer, and Vishruth Girish, a former CSHL research technician currently working on his M.D. and Ph.D. at Johns Hopkins University.
Now at Yale University, Sheltzer reflects on how cancer research has shifted focus over time. 鈥淢any early biologists thought aneuploidy caused cancer,鈥 he says. 鈥淎s the 20th century progressed, this view fell out of fashion. DNA sequencing found that tumors had mutations in individual genes, and cancer was attributed to these mutations. We still knew aneuploidy was present. It was just hard to study or manipulate, so it was treated like a bystander during cancer development.鈥
To settle once and for all whether aneuploidy was a mere bystander, the researchers came up with a new genome-editing technique on a scale never before achieved. Over the past decade, scientists have been able to delete individual genes or pieces of DNA using molecular 鈥渟cissors鈥 known as CRISPR. But with the new technique, called ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), they can now slice off an entire arm of a chromosome. That could mean erasing over a thousand genes at once.
The team found that when aneuploidies are deleted from cancer cells, it cripples them. The malignant cells aren鈥檛 able to grow as fast and can no longer form tumors. 鈥淪o, the aneuploidy in cancer cells isn鈥檛 just a bystander,鈥 Sheltzer says. 鈥淚t鈥檚 actually central for malignant growth, just like the 19th-century pathologists thought.鈥
Amazingly, ReDACT appears effective across a wide range of cancers, including breast, ovarian, and gastric cancer and melanoma. 鈥淲e went at it in a cancer-agnostic manner,鈥 explains Lakhani, now a postdoctoral researcher in CSHL Professor & HHMI Investigator Rob Martienssen鈥檚 lab. Lakhani says:
鈥淲e鈥檝e made these tools publicly available. Hopefully, people will take these techniques and study their favorite chromosome, and will learn across all cancer types what the relative contribution of each aneuploidy is to tumor development. Perhaps that leads to more therapies.鈥
Lakhani thinks this work could open the door to personalized cancer treatments. 鈥淵ou can imagine if patients exhibit an extra copy of a chromosome in their tumors, perhaps they鈥檙e more likely to respond to therapies,鈥 he says, 鈥渁s opposed to patients who have the same tumor but not an extra copy.鈥 If proven, this hypothesis could help guide the future of cancer therapeutics.
CSHL has a long . With time, Lakhani, Sheltzer, and Girish鈥檚 work might yet go down as another major breakthrough. Beyond the annals of science, their discovery may someday lead to better outcomes for countless cancer patients. Such an achievement would be truly historic.
Written by: Luis Sandoval, Communications Specialist | [email protected] | 516-367-6826
鈥淭丑别 Flow Cytometry Shared Resource offers researchers equipment, training, and assistance with cellular analysis for a variety of applications as well as cell sorting. Our staff oversees equipment maintenance and quality control, trains new users on instrument operation, and assists with assay development and data analysis. We also provide tissue culture facilities for sample preparation and cell maintenance during ongoing flow cytometry experiments.鈥 鈥 Director Pamela Moody