Identifying Breast Cancer Targets using High-Throughput NGS

Introduction

Alex Swarbrick, PhD and his colleagues at the Garvan Institute of Medical Research initiated the Breast Cancer Atlas Project to catalog genomic and protein data from more than one million individual breast cancer cells. Together with tissue pathology data, this state-of-the-art reference database will assist researchers and clinicians in identifying breast cancer targets for therapeutic and diagnostic development, and in making more precise treatment decisions in the future.

“We often view cancer biology through the lens of pathology,” Dr. Swarbrick said. “For more than a decade, many of the major and transformational discoveries in breast cancer have come through that field, including the discovery of diagnostic biomarkers to help with the stratification of disease. By combining our interest in pathology and the emergence of new next-generation sequencing (NGS)-based approaches, we realized that there was an opportunity to understand the cellular composition of breast cancers at a high resolution.”

Cellular Genomics in Breast Cancer

Dr. Swarbrick uses cellular genomics techniques to understand and identify stromal–epithelial signaling in tumor microenvironments. Many of the drivers for epithelial cancers, such as breast cancer, are receptors activated by sensing ligands on the outside of the cell in the extracellular space. The tumor microenvironment is an abundant source of these ligands.

Together with clinical collaborators in medical oncology, pathology, surgery, and radiology, Dr. Swarbrick started a program to collect fresh tissue samples from several hospitals in Sydney, Australia. With visionary funding support from the National Breast Cancer Foundation, the Breast Cancer Atlas Project was founded to generate a comprehensive cellular atlas of breast cancer.

Specialized Tissue Collection Approach

“We’ve been collecting and storing tissues for 4–5 years in a way that is compatible with cellular genomics,” Dr. Swarbrick stated. “It’s a new bioresource that underpins our program.”

The team has completed tissue pathology studies for more than 250 samples. “We can now start to generate the cellular genomic data quickly using the NovaSeq 6000 System,” Dr. Swarbrick said. “We’ve commenced that project and are now about 15% of the way in.

"We’ve shifted to the NovaSeq 6000 System for our own cellular genomics studies because of the efficiencies and economies it affords.”

“Part of the value is that we’ve been collecting clinical and histopathological variables along with the cellular genomic data,” Dr. Swarbrick added. “The power of having a large cohort is that we can begin to relate the cellular and molecular features that we find with the clinical features and outcomes of those patients.”

NGS Powers Cellular Genomics Studies

In the early days of their cellular genomics studies, Dr. Swarbrick and his team used the NextSeq™ 500 System. “The NextSeq 500 System is agile, quick, and relatively easy to operate,” Dr. Swarbrick said. “It allowed us to generate data quickly. When a new sample came in, we could capture it, sequence it, and have the data within days.”

The team chose to adopt the NovaSeq 6000 System to handle high-capacity sequencing projects, such as the Breast Cancer Atlas. “We’ve shifted to the NovaSeq 6000 System for our own cellular genomics studies because of the efficiencies and economies it affords,” Dr. Swarbrick stated. “All our single-cell RNA sequencing (scRNA-Seq) is performed on the NovaSeq 6000 System. We still use the NextSeq 500 System for our Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) studies to measure protein levels on the surface of single cells.”

Read more about these studies:

Garvan Institute iCommunity article

Learn more about the solutions mentioned in this case study:

NovaSeq 6000 System

NextSeq 500 System: This system has been discontinued. We suggest the NextSeq 1000 and 2000 Systems as alternatives.

Single-Cell RNA Sequencinq