A complete and comprehensive mapping of healthy breast cells is now available on-lineIt is a new tool for investigating how Breast cancer develops and the differences in breast tissue in different genetic ancestors.
Harikrishna Nakshatri, PhD, lead author of the study, said Insights into precision medicine that although there have been previous studies on normal breast tissue, their study is unique.”We used breast tissue from women who were clinically free of breast cancer. Other studies have used samples from breast reductions, which we and others have shown to be histologically abnormal. Our study included samples from women of different genetic backgrounds, so the data are applicable to all people.”
In an article published this month in Natural medicinethe researchers present a comprehensive atlas of breast tissue cells – including details of how the genome is organized in each cell type and how that genome organization affects how each cell type makes RNA to control its function in different parts of the breast – using healthy breast tissue from women of different ancestry.
“Breast cancer shows different outcomes depending on genetic lineage,” Nakshatri said. “Socioeconomic factors are certainly a contributing factor, but we believe biology and ancestry also play a role. This study will help us explore that biological, ancestry-related aspect.”
Nakshatri’s lab sequenced 88,000 cell nuclei from 92 women who donated healthy breast tissue to the Komen Tissue Bank at the IU Simon Comprehensive Cancer Center. The donors included people of African, European, Native American, Hispanic, East Asian, Southeast Asian and Ashkenazi Jewish European descent.
Cell mapping includes data not only on the genes expressed in different cell types, but also on how the genes are organized and which specific gene expressions are restricted to each cell type. Researchers know that breast cancer most often arises in certain cell types and that its location of origin leads to different cancer types and treatment responses. This study could improve the understanding of breast cancer development and lead to the identification of new treatment targets.
“The goal of this research was to understand the building blocks of the normal breast – that is, how many different cell types are present in the normal breast and whether there is genetic variability in the building blocks of the cells,” Nakshatri said. “Until we know which cell types in the breast give rise to cancer, we can’t really figure out exactly what goes wrong in breast cancer compared to the normal breast.”
Until now, normal tissue from breast cancer surgery and breast reduction surgery has been used for research. The Komen Tissue Bank, the world’s only bank of healthy breast tissue, provided IU researchers with a unique opportunity for this study.
“We use tissue from women who are clinically free of breast cancer. Because of this, we believe the data we’ve generated is nearly perfect — really as close as you can get,” Nakshatri said. “The data we’ve generated from this will last forever because it will be used by many, many groups for future research.”
They also have several types of useful data, he said, including: extensive analyses of lobular and ductal epithelial cells, data from the same donor but whose tissues were collected 10 years apart, a gene expression pattern and a relationship between gene expression and chromatin organization.
Nakshatri is the Marian J. Morrison Professor of Breast Cancer Research at the IU School of Medicine and an investigator at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Simon Comprehensive Cancer Center.
The cell atlas information from the study will be widely available to breast cancer researchers through National Institutes of Health databases. Human Cell Atlas, CELLxGENEAnd Natural medicine.
