In a recent study published in the journal Nature, researchers in the BC Cancer Laboratory of UBC Professor Dr. Samuel Aparicio, in collaboration with the lab of Dr. Sohrab Shah at Memorial Sloan Kettering Cancer Center (MSKCC), used a single cell sequencing platform developed at BC Cancer, called Direct Library Preparation (DLP+) to sequence more than 35,000 genomes from engineered cell lines as well as tumour tissue samples donated from patients with Triple Negative Breast Cancer (TNBC) and High-Grade Serous Ovarian Carcinoma (HGSC). These two types of cancer are known for their genomic instability, making them particularly challenging to study and treat.

The UBC and MSKCC team aimed to better understand the genomic variation that occurs within these types of cancer and how this variation may contribute to the progression and evolution of the disease. By sequencing the genomes of individual cancer cells, the researchers identified distinct 'foreground' mutational patterns defined by cell-to-cell structural variation occurring in the 'background' of cancer-associated genomic instability. These patterns were found to significantly contribute to the origins of phenotypic and evolutionary diversity of TNBC and HGSC, revealing previously hidden genomic states of cancer cells.

One of the key findings of the study was the presence of high-level amplifications of chromosomal segments, including regions containing cancer-causing oncogenes, in single cells as well as across clonal populations. These amplifications were more prevalent in a genomic subset of both TNBC and HGSC tumours, characterised by fold-back inversion (FBI) chromosomal patterns, and were associated with poorer survival.

The study also identified parallel allele-specific alterations, whereby cells with identical copy numbers at a given chromosomal region displayed different combinations of maternal or paternal alleles. These variations were associated with evolutionary diversity and may help explain how cancer cells can evade and resist cancer therapies. Additionally, the researchers identified a novel type of foreground structural mutation in human cancers, called "serrate structural variation" (SSV), characterised by progressive accumulation or erosion of chromosome regions from cell to cell.

"These 'serrated' regions are especially prevalent in a subset of ovarian and breast cancers associated with poor survival," says Dr. Ciara O'Flanagan, a Research Associate within the Aparicio Lab and one of the lead authors of the study. "This discovery has important implications for understanding the evolution and treatment of these aggressive cancers."

By capturing these mutations in single cells as they arise, the researchers were able to gain a more detailed and nuanced understanding of how cancer cells evolve.

Overall, this study provides new information about the genomic variation that occurs within TNBC and HGSC, and how this variation may contribute to the progression and evolution of the disease. By capturing these mutations in single cells as they arise, the researchers were able to gain a more detailed and nuanced understanding of how cancer cells evolve. These findings may underlie how cancer cells evade and resist cancer therapies.