Navin is grateful to the foundation for support of the project, which he agrees is high-risk, high-reward because it aims to break new ground in the genomic analysis of cancer.
First, he must develop tools to reliably isolate individual cancer cells and identify mutations in all of the genes that encode proteins. Then he will apply single-cell gene sequencing to triple-negative breast cancer, the most lethal form of the disease.
Develop tools, apply them to triple-negative breast cancer
"Most of the tools we have now operate on bulk tumor tissue samples, which include normal supportive cells, or stroma, and immune system cells as well as cancer cells, which have different genetic mutations," Navin said. "So when we analyze tissue in bulk, we find the average genetic signal of the tumor. What you miss are the rare cells that may be most malignant."
Identifying these cells is particularly important for those with triple-negative breast cancer, which does not have the three protein targets that make other breast cancers much more treatable.
"Triple-negative breast cancer is the most aggressive type, with lowest survival rates, the most intratumor genetic heterogeneity, and it metastasizes the most," Navin said. "So there's really a dire need to help these patients by developing new therapies to inhibit metastasis."
To sequence the full coding regions of each single cell, Navin's lab will isolate single cells that have naturally doubled their chromosome content. The cell will be dissolved and the DNA will be expanded from picogram (trillionth of a gram) to nanogram (billionth) quantities using whole-genome amplification. This will provide sufficient material to generate libraries for 'next-generation' sequencing on the Illumina platform.
From this data, the full set of coding mutations can be detected in each cancer cell and
|Contact: Scott Mervilloe|
University of Texas M. D. Anderson Cancer Center