Optical genome mapping: technical basis and applications in hematological malignancies

Abstract

Cytogenomic analyses of hematological malignancies require the use of different techniques, whether combined or on isolation, for the detection of chromosomal abnormalities. Optical genomic mapping (OGM) is a new technology based on the analysis of long DNA molecules fluorescently labelled in specific sequences that create a unique pattern, allowing the simultaneous detection of numerical and structural abnormalities with higher sensitivity (up to 5%) and precision than karyotyping. The aim of this review is to describe the methodological and analytical basis of OGM, present the most relevant findings published to date, and raise future challenges regarding its implementation in diagnostic laboratories. Multiple studies have shown that OGM will potentially allow the cytogenetic approach of patients in a single test offering higher resolution (5 Kb vs 5-10 Mb) and better characterization of abnormalities than conventional techniques. This technique also presents some limitations such as a sensitivity limited to 20% for copy number alterations, or the inability to detect rearrangements affecting centromeric and/or telomeric regions. Its implementation in the routine diagnosis practice will require standardization of analysis criteria, validation of many of the new abnormalities identified through the technique, and comparative prospective studies to define in which entities and situations it can complement and/or replace the current methods.