On Day 3 of Bionano Genomics 2022 Symposium, world-leading experts discussed the application of optical genome mapping (OGM) in solid tumors.

Precision medicine is rapidly becoming the norm in oncology clinical management, spurred in large part by the rapid advances in genomics over the past decade. Precise knowledge of genomic aberrations in a tumor is required to understand its pathophysiology, enable diagnosis and guide targeted therapy decisions.

Challenges in determining the genomic characteristics of a tumor can be broadly categorized as technical and biological. Conventional cytogenetic and molecular analysis techniques have limitations in their ability to accurately detect genomic patterns efficiently, in a cost-effective manner, and with a reasonable amount of precious tumor tissue. Biological challenges are primarily related to the complexity of tumors. Intertumor and intratumor heterogeneity caused by genetic modifications presents significant hurdles in the clinical setting.

Evidence has demonstrated that OGM workflows can be scalable and can address an unmet need by providing increased resolution and shorter turnaround times over traditional techniques in the evaluation of solid tumors. Dr. Ravindra Kolhe, from the Medical College of Georgia at Augusta University, showed data from an ongoing study to characterize 100 solid tumors, where OGM using Saphyr^® demonstrated clinical utility for chromosomal analyses, over karyotyping, fluorescence in situ hybridization, and microarray. Based on these findings, Dr. Kolhe and his team are working on a CLIA validation study for OGM and its subsequent incorporation into their clinical laboratory workflow.

Two independent studies showed that pediatric brain tumors can be rapidly characterized by OGM. Dr. Elena Garcia Sanchez, researcher at the Hospital Infantil Universitario Niño Jesús in Madrid, Spain presented a case study about a 13-year-old with a mediastinal mass that could not be diagnosed using routine tests. Running pleural effusion samples using OGM on Bionano’s Saphyr^® platform, the team was able to diagnose alveolar rhabdomyosarcoma and initiate therapy. On clinical improvement, the mass was biopsied, and histopathology confirmed the diagnosis that was made earlier using OGM. OGM showed concordance with traditional testing and was shown to be a potential important tool for detecting solid tumors that are inaccessible by routine biopsies. While most cancers are clinically challenging, brain tumors represent a particularly intractable group, and within pediatric brain tumors, SVs play an important role. Dr. Miriam Bornhorst, from Children’s National Hospital, initiated a project to determine a more reliable approach for detection of SVs in pediatric brain tumor samples. Dr. Bornhorst’s project demonstrated that OGM can be an effective method for the identification of clinically relevant SVs, some of which are not detected with other clinical testing methods. Further clinical studies are ongoing to determine the effect of SVs on responses to treatment and prognosis in pediatric brain tumors.

OGM can also provide insight into the genetic variations in a wide range of solid tumor types, including pulmonary mesothelioma and undifferentiated small round cell sarcomas. Mesothelioma is a slow growing cancer of the pulmonary mesothelium that is caused by asbestos or other particulate fibers. It is a challenging cancer to work with and to obtain DNA from owing to the fibrotic nature of the tumor. Dr. Matthew Couger, lead investigator at Brigham and Women’s Hospital, has been testing Bionano’s OGM workflow for genomic characterization of mesothelioma samples. Using OGM, Dr. Couger and his team were able to obtain high-fidelity data to decipher the complex chromosomal landscape. Similarly, Dr. Juan Diaz-Martin from the Department of Pathology-HUVR and Instituto de Biomedicina de Sevilla presented his findings on undifferentiated small round cell sarcomas (USRCS), a highly aggressive cancer. This data demonstrated comprehensive characterization of genomic aberrations using OGM that could have a significant impact on clinical outcomes.

New applications of OGM can help solve long-standing challenges in genetic discovery. Inherited forms of breast cancer have been well-established in the medical literature. However, despite routine evaluation, the causative variant cannot be identified in some high-risk breast cancer cases. Dr. Tuomo Mantere, from University of Oulu, Finland, presented data using OGM to identify new SVs in breast cancer genes in these high-risk families. In a separate example, Dr. Gopalrao Velagaleti, from University of Texas Health, discussed work using OGM to authenticate and characterize cell lines for research laboratories. Working with contaminated and unauthenticated cell lines impacts research and can have a significant cost in research dollars. Dr. Velagaleti concluded that OGM’s high resolution and short turnaround times can make it more cost-effective for authenticating and characterizing cell lines as compared to traditional methods.

“We continue to be pleased with the growing number of potential applications of OGM in the investigation of solid tumors,” said Alka Chaubey, PhD, FACMG, chief medical officer at Bionano. “Today’s sessions really demonstrate how OGM can help overcome the limitations of traditional methods and provide genetic characterization of tumors that impact clinical decision-making and improve cancer care.”

Here are the presenters from Day 3:

Elena Garcia Sanchez, PhD

Researcher at the Hospital Infantil Universitario Niño Jesús in Madrid, Spain

“Optical Genome Mapping Application for Diagnosis of Non-Haematological Cancers”

Tuomo Mantere, PhD

Cancer and Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, Finland

“Optical Genome Mapping in Unexplained High-risk Breast Cancer Families”

Gopalrao Velagaleti, PhD

Professor and Director, Department of Pathology and Laboratory Medicine, UT Health – San Antonio

“Vigor and Reproducibility in Research: The Cell Line Saga: Is OGM the Answer?”

Miriam Bornhorst, MD

Clinical Director Gilbert Family Neurofibromatosis Institute, and Medical Director Cancer Genetics Program, at Children’s National Hospital in Washington, DC

“Optical Genome Mapping Reveals Novel Structural Variadnts in Pediatric Brain Tumors”

Matthew Couger, PhD

Lead Investigator at Brigham and Women’s Hospital

“The Chromosomal Landscape of Mesothelioma”

Juan Diaz-Martin, PhD

Molecular Biologist, Department of Pathology-HUVR and Instituto de Biomedicina de Sevilla (IBiS)

“Complex Chromosomal Rearrangement Patterns in Undifferentiated Small Round Cell Sarcomas Associate with Poor Clinical Outcome”

Ravindra Kolhe, MD, PhD, FCAP

Associate Dean for Translational Research Medical College of Georgia at Augusta University

“Utility of Optical Genome Mapping for the Chromosomal Characterization of Solid Tumors”

Symposium wraps up tomorrow with a session on OGM in combination with next-generation sequencing (NGS). Register now to join us live and view recorded sessions on-demand.