Guiding the global evolution of cytogenetic testing for hematologic malignancies

Abstract

Cytogenetics has long represented a critical component in the clinical evaluation of hematologic malignancies. Chromosome banding studies provide a simultaneous snapshot of genome-wide copy number and structural variation, which have been shown to drive tumorigenesis, define diseases, and guide treatment. Technological innovations in sequencing have ushered in our present-day clinical genomics era. With recent publications highlighting novel sequencing technologies as alternatives to conventional cytogenetic approaches, we, an international consortium of laboratory geneticists, pathologists, and oncologists, describe herein the advantages and limitations of both conventional chromosome banding and novel sequencing technologies and share our considerations on crucial next steps to implement these novel technologies in the global clinical setting for a more accurate cytogenetic evaluation, which may provide improved diagnosis and treatment management. Considering the clinical, logistic, technical, and financial implications, we provide points to consider for the global evolution of cytogenetic testing.

High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance

“…However, CBA has limited resolution and poor sensitivity in detection of some clinically actionable alterations, and on occasions, can be non-informative due to the requirement of cell culture. In these contexts, and in the setting of failed or insufficient metaphases, as recommended by NCCN, these findings need to be supplemented with additional assay(s) such as fluorescence in situ hybridization (FISH) and chromosomal microarray (CMA), resulting in increasing costs and turn-around-times for the laboratory [ 22 – 24 ]. As a result, the knowledge of the full spectrum and prevalence of genome-wide high-resolution chromosomal SVs in MDS remains limited.…”

Molecular cytogenetics in acute myeloid leukemia in adult patients: practical implications

“…Patients who do not carry any of the aforementioned defining genetic alterations or whose pretreatment cytogenetic investigation fails are categorized into AML subtypes defined by differentiation [7]. Notably, unsuccessful cytogenetic assays are rare, occurring in 2-6% of patients in large studies [68,69].…”

“…Duncavage et al [99] demonstrated the clinical utility of WGS for the evaluation of patients with AML and suggested WGS to be an alternative to cytogenetic analysis of myeloid malignancies. The advantages and limitations of this and other novel technologies [100] in hematologic malignant disorders have been recently reviewed in depth by Akkari and colleagues [68]. The authors discussed clinical, logistic, technical, and financial implications and concluded that although clinical usefulness of WGS is undisputable, the implementation of WGS technology by clinical laboratories worldwide is currently unlikely.…”

High-Throughput CRISPR Screening in Hematological Neoplasms

“…Taking into account that copy number (CN) events are usual in hematological malignant diseases [ 135 ] and that recent studies have shown the increase of false positive relevant genes in CRISPR screening due to CN, some algorithms have been designed to solve this problem such as CRISPy [ 136 ], CRISPRcleanR [ 137 ], and CERES, which has been implemented in the Broad DepMap project [ 131 ].…”