New Breast Cell Atlas Enhances Understanding of Cancer Origins

Scientists at the Melvin and Bren Simon Comprehensive Cancer Center at Indiana University have recently completed the largest mapping of healthy breast cells. These results provide a valuable resource for IU and other researchers studying the phenotypic variations in breast tissue across genetic lineages and the pathogenesis of breast cancer.

Using healthy breast tissue from women of diverse ancestry, researchers created a comprehensive atlas of breast tissue cells published in Nature Medicine. The atlas includes details on how the genome is organized in each cell type and how this organization affects how RNA is made in each cell type to drive their function in various parts of the breast.

Breast cancer shows variability in the outcome based on your genetic ancestry. While socio-economics is certainly a contributing factor, we believe biology and ancestry also play a role. This study will help us to address that biological, ancestral aspect.”

Harikrishna Nakshatri, Ph.D., Study Senior Author, Indiana University

In addition to being a researcher at the IU Simon Comprehensive Cancer Center's Vera Bradley Foundation Center for Breast Cancer Research, Nakshatri holds the Marian J. Morrison Professor of Breast Cancer Research at the IU School of Medicine.

Nakshatri's group sequenced around 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 had African, European, Indigenous American, Hispanic, East Asian, Southeast Asian, and Ashkenazi-Jewish-European ancestors.

In addition to information on the genes expressed in different cell types, cell mapping also provides information on the arrangement of genes and whether particular gene expressions are unique to a given cell type.

Researchers are aware that certain cell types are the primary sites of breast cancer initiation and that the location of origin influences the type of cancer and the response to treatment. This research may lead to novel therapy targets and a better knowledge of the pathogenesis of breast cancer.

This research aimed to understand the building blocks of the normal breast—meaning how many different cell types exist in the normal breast and do the building blocks of the cells show genetic ancestry-dependent variability. Unless we know from which cell types of the breast the cancer originates, we cannot figure out what exactly is going wrong in breast cancer compared to the normal breast.”

Harikrishna Nakshatri, Ph.D., Study Senior Author, Indiana University

Prior study materials have included reduced mammography samples and normal tissue from breast cancer surgery. IU researchers have a special chance for this investigation, thanks to the Komen Tissue Bank, the only healthy breast tissue bank in the world.

We are using tissue from women who are clinically free of breast cancer; for that reason, we do believe the data that we created are close to perfect truly the closest you can get. The data we generated from this is going to stay in perpetuity because it is going to be used by many, many groups for future research.”

Harikrishna Nakshatri, Ph.D., Study Senior Author, Indiana University

Researchers studying breast cancer will have wide access to the study's cell atlas data via databases provided by the National Institutes of Health, Human Cell Atlas, and Chan Zuckerberg CELL by GENE Discover.