Breast cancer is one of the most complex diseases to study because tumors are not made up of identical cells. Instead, they contain different subpopulations of cells that can change over time. Understanding how these differences arise and how they affect cancer progression is critical for developing better treatments.

A team led by researchers from the UT MD Anderson Cancer Center has developed a powerful new method called wellDR-seq. This approach allows scientists to study both the genome (DNA) and transcriptome (RNA) from the same single cell, providing a clearer picture of how genetic changes influence gene activity.

Using wellDR-seq, the team analyzed more than 33,000 cells from 12 estrogen-receptor-positive breast cancers. They found ancestral subclones in several patients that showed hormone-responsive features, pointing to a possible origin of the cancer. Importantly, the method revealed how changes in DNA copy number relate to gene expression. While some genes showed predictable, linear relationships, others varied greatly, even within the same chromosomal region.

“WellDR-seq is an exciting new technology that enables us to simultaneously measure DNA and RNA in the same cells to understand how chromosomal changes in breast cancer impact gene expression and lead to cancer progression.” Nicholas Navin, Ph.D. – Systems Biology

The findings shed light on the intricate connections between DNA structure and gene activity in breast cancer. By linking genetic alterations to their effects at the single-cell level, wellDR-seq opens the door to more precise insights into how tumors evolve and why they behave differently across patients.

Source – MD Anderson Cancer Center