For the study, researchers sought to understand the prevalence of copy number alterations in normal tissues. They examined tens of thousands of breast cells from 28 women using advanced single-cell gene sequencing technology developed by researchers at UBC and BC Cancer, known as DLP+. Although genetic alterations were detected at very low levels in most of the women studied, they were only detected in the luminal cells that line the lobules and ducts through which milk circulates in the breast, not in the associated contractile cells.
“Since luminal cells are thought to cause all major types of breast cancer, the fact that these genetic alterations accumulate specifically in luminal cells provides further support for the hypothesis “That these alterations may prepare or predispose these cells to the development of cancer,” adds co-senior author Dr. Joan Brugge, professor of cell biology at Harvard Medical School.
“This study represents an important step in our collective quest as scientists to understand the earliest events in the development of breast cancer. These our knowledge can inform our efforts to design new, more effective prevention and monitoring strategies for people at high risk of cancer,” he says.
Most of the mutated cells contained only one or two copy number changes, and it is known that multiple mutations are necessary to form cancer. However, in some women carrying high-risk genetic variants of BRCA1 and BRCA2, researchers observed “extreme” examples of cells harboring six or more of these important genetic changes. These extreme cells could represent another step in the process of cancer development, suggesting a possible pathway for progression from normal cells to cancer cells in high-risk individuals.
“To study this phenomenon, we used a method originally developed to study genome instability in cancer, which provides a comprehensive view of copy number alterations at the gene level.” individual cells”argues the doctor Sohrab Shahholder of the Nicholls-Biondi Chair in Computational Oncology and Head of Computational Oncology at MSK. “Our computational approaches further allowed us to identify and analyze these rare events that are not visible with standard sequencing assays.”
