New DNA sequencing technique may help unravel genetic diversity of cancer tumors

June 25, 2020

The ability to sequence the genome of a tumor has revolutionized cancer treatment over the last 15 years by identifying drivers of cancer at the molecular level. But understanding the genetic diversity of individual cells within a tumor and how that might impact the disease progression has remained a challenge, due to the current limitations of genomic sequencing.

Using a microfluidic droplet based single cell sequencing method, USC researchers have simultaneously sequenced the genomes of close to 1,500 single cells, revealing genetic diversity previously hidden in a well-studied melanoma cell line.

The study, just published in Nature Communications Biology, demonstrates the ability of single-cell sequencing to reveal possible evolutionary trajectories of cancer cells.

"We used this approach to examine a standard cancer cell-line, examined thousands of times by many different labs," said David Craig, PhD, co- director of the Institute of Translational Genomics at Keck School of Medicine of USC and study author. "What was really surprising here, was with this technology we uncovered complexity we did not expect. This line actually consistently became a mixture of different types of cells. Reexamining decades of prior work on this line - now with this new information - we have new insights into tumor evolution."

Getting a high-resolution view of cancer's complexity

Currently, the genetic information of a tumor is typically obtained by sequencing millions of tumor cells together, rather than individually. While this method offers a broad view of the genetic makeup of the tissue it can miss small populations of cancer cells within a tumor that are different from the majority of cells.

With other approaches that analyze the DNA of individual cells, the process is laborious, taking weeks to process just a few cells and requiring resources that most laboratories do not have.

For this study, researchers used an emerging technique called "single-cell copy number profiling." developed by 10X Genomics with novel analysis methods that integrated these results with those of historical methods.

"Instead of analyzing tissue DNA that is the average of thousands of cells, we analyzed the individual DNA of close to 1500 cells within a single experiment," said Dr. Enrique Velazquez-Villarreal, lead author and assistant professor of translational genomics at Keck School of Medicine at USC. "Studying cancer at this higher resolution, we can discover information that lower-resolution bulk sequencing misses."

Their analysis revealed at least four major sub-populations of cells, also known as clones, that are expected to have, at some point during the cancer cell line's evolution, mutated from the original cancer cell.

The ability to identify sub-clones in cancer tissue could provide important biological insights into how cancer progresses, how it spreads and why it can become resistant to treatment.

"What if there's a small population of cells in a tumor that has acquired a change that makes them resistant to therapy? If you were to take that tumor and just grind it up and sequence it, you may not see that change," said John Carpten, PhD, study author and Co-Leader of the Translational and Clinical Sciences Program at the USC Norris Comprehensive Cancer Center, Chair of the Department of Translational Genomics, Keck School of Medicine, and Co-Director of the USC Institute for Translational Genomics. "If you go to the single cell level, you not only see it, but you can see the specific population of cells that has actually acquired that change. That could provide earlier access to the molecular information that could help define treatment approaches."

The researchers plan to share their data in the hope that more cancer researchers will focus on single-cell sequencing. They are also using their technique to study genetic diversity in clinical cancer specimens as a way to better understand the early molecular changes that lead to aggressive and tough-to-treat advanced cancers.
-end-
About this study

In addition to Craig, Velazquez-Villarreal and Carpten, the study other authors include Shamoni Maheshwari, Jon Sorenson, Ian T. Fiddes, Vijay Kumar, Yifeng Yin, and Claudia Catalanotti of 10x Genomics; and Mira Grigorova of Hutchison-MRC Research Centre, University of Cambridge; and Paul A. Edwards of Hutchison-MRC Research Centre, University of Cambridge and Cancer Research UK Cambridge Institute.

This study was supported by 10x Genomics, the Norris Comprehensive Cancer Center, and the Department of Translational Genomics at Keck School of Medicine of University of Southern California.

Keck School of Medicine of USC

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.