Bionano Genomics Data is a Key to Understanding Cancer Genome Structures That Make Tumors Grow Aggressively

Nature Communications paper describes circular genome structures that make cancers like glioblastoma multiforme, the cancer that killed senators Ted Kennedy and John McCain, so deadly

SAN DIEGO, Sept. 02, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced today a study published in the journal Nature Communications used its genome imaging technology to increase understanding of the genome structures that make tumors like glioblastoma multiforme, lung cancer and Chronic Myeloid Leukemia (CML) so aggressive. By combining Bionano’s Saphyr data with sequencing data using custom developed software, a team led by Professor Vineet Bafna of the University of California San Diego (UCSD) was able to reconstruct circular pieces of genetic material in cancer cells that allow the tumor to grow much more rapidly. The increased understanding of these circular DNA fragments can help in the development of targeted therapies, enable better classification of cancer subtypes, and contribute to a more efficient use of existing drugs by enabling truly personalized medicine.

For cancers to grow rapidly and escape the various mechanisms of the cell and immune system to keep malignant cell growth under control, they typically show mutations that disable the genes that inhibit replication of the cell and make extra copies of genes that stimulate replication of the cell. These extra copies of growth-enhancing genes are called oncogene amplifications, and they enable rapid tumor evolution and the rewiring of regulatory circuitry in the cell. These amplifications can happen inside the chromosomes that carry the oncogenes, but often they occur outside of the chromosomes, in circular mini-chromosomes called extra-chromosomal circular DNA, or ecDNA. Because these ecDNA structures are much smaller than regular chromosomes, they can replicate quickly and form a mechanism for the tumor to increase the speed with which it can replicate, grow, and spread.

To date, ecDNA structures have been difficult or impossible to fully characterize due to their complex and repetitive nature, containing numerous copies of the same genes side by side in structures that are difficult or impossible to resolve with short-read sequencing like NGS. By developing software called AmpliconReconstructor that combines NGS reads with optical mapping data generated by Saphyr, the UCSD team was able to fully resolve the ecDNA structures found in various cancers such as glioblastoma multiforme and lung cancer. Additionally, the team was able to resolve a chromosomal aberration called the Philadelphia Chromosome, the target of the first targeted cancer therapy Gleevec, and the structure of oncogene amplifications in kidney cancer, breast cancer and various other cancer cell lines.