What is the difference between genetic variants of the same cancer tumor?

Just as no two people have the same genetic makeup, in breast cancer patients, no two tumors have the same genome of cells. According to a recent study, different breast cancer subtypes also have a wide variety of variant tumors. This finding has important implications for the diagnosis and treatment of breast cancer and could help breast cancer patients who develop chemoresistance. A related paper was published in the recent issue of Nature. The study was conducted by the Nicholas K. Narwin’s research group. They have developed a new sequencing method called “nuclear sequencing” that sequences the genome of a single cell, which, when combined with single-cell molecular sequencing, can analyze thousands of cells, according to a recent report by PhysOrg.com. In fact, the growth rate of different tumor cells varies greatly. “We found two very different ‘molecular clocks’ operating at different stages of tumor growth.” Navin said, “Triple-negative breast cancer tumor cells have a variable rate of growth, while estrogen receptor-positive (ER+) breast cancer tumor cells do not.” About 75 percent of breast cancers are ER+ and will grow with increasing estrogen, and estrogen therapy is usually used for these patients. Triple-negative breast cancers account for about 15 to 25 percent of all breast cancers and usually do not respond to hormone therapy or standard chemotherapy. “A common problem in the field of single-cell genomics is the inability to identify the variants detected in individual cells.” To deal with this problem, we combined single-cell sequencing with targeted single-cell deep sequencing,” said Yong Wang, first author of the paper and a postdoctoral fellow in the Department of Genomics. This not only confirms the variants, but also accurately detects the frequency of variants in thousands of cells.” And the important question in chemotherapy is whether certain cellular variants in tumors are resistant variants, i.e., treatment-induced variants. “While this issue has been studied in bacteria for decades, it is still poorly understood in most human cancers.” Navin said, “Our data show that a large number of diverse variants are present in tumor cells even before chemotherapy. We therefore expect that genomic diversity testing will serve as a prediagnostic tool to identify which patients are likely to develop chemoresistance.” The researchers noted that large population sequencing studies of breast tumors have identified many major variants, but little is known about the diversity of variants. This study adds to the understanding of “genomic diversity” within tumors. Genomic diversity is useful in clinical settings to predict tumor invasion, metastasis, and patient survival.