UZ Leuven

Routine genetic analysis of hematologic cancers involves karyotyping and fluorescent in-situ hybridization, two techniques that can detect structural and numerical abnormalities in chromosomes. These tests however are laborious, time-consuming and not always successful. Karyotyping for example relies on successful culturing of cancer cells, requiring sufficient and fresh biopsy material. Optical genome mapping (OGM) is a new technology that provides similar information as classical tests but with a simplified workflow and without the need for cell culture. The Center of Human Genetics (University Hospitals Leuven) introduced OGM in 2021 as a routine genetic test for patients diagnosed with acute leukemia and validation of OGM in non-Hodgkin lymphoma is currently ongoing. Interestingly, OGM revealed the presence of many unknown genetic variants in patients with leukemia/lymphoma. Evidence from other research groups similarly suggests that OGM can detect additional structural and numerical abnormalities in genetic material from cancer patients. These variants however are not necessarily malignant, but could represent normal genetic variation between human beings. To discriminate clinically relevant results from benign variation, we intend to consult publicly available databases and to investigate if the variants are located in areas related to (hematologic) cancer. We also plan to examine the occurrence of the variants in OGM data from a control population comprised of patients with no hematologic disorders. Only variants highly specific to the cancer population are verified using additional genetic tests, before the presence of the variant is confirmed in a second independent cohort of patients with the same type of leukemia/lymphoma. All these steps are needed to ensure that only variants that play a role in the disease mechanism or that predispose to the development of leukemia/lymphoma are retained.