Karyotypic analysis has been invaluable for detection of chr

Karyotypic analysis has been invaluable for detection of chromosomal rearrangements specific to certain diseases, such as t(9;22) in CML and t(15;17) in acute promyelocytic leukemia [4,5], and can predict sensitivity to molecularly targeted drugs, such as imatinib in CML [16]. Cytogenetics have been part of the revised International Prognostic Scoring System (IPSS-R) and shown to have important prognostic implications in MDS patients, with detection of 5q- syndrome being a prominent example [6]. Whole CT99021 scanning studies, such as CMA using SNP arrays, eliminate the need for dividing cells, have a much higher level of resolution than karyotypic analysis, and allow for detection of both DNA copy number and LOH throughout the genome in a single experiment [7]. CMA also uncovers acquired cn-LOH, which is indicative of somatic uniparental isodisomy. While cn-LOH occurs commonly in hematological malignancies [8], it is undetectable by classical cytogenetics [7,9]. Such was the case in our patient, in which CMA of peripheral blood demonstrated isodisomy of 17p, a site encompassing the TP53 tumor suppressor gene. Notably, recurrent mutations of TP53 have been previously described in myeloid malignancies [8]. While this report demonstrates that CMA with SNP arrays is useful for the analysis of genomic imbalances in the peripheral blood of patients with suspected MDS, this technique is not readily available at many medical centers and many institutions perform fluorescence in situ hybridization to detect cytogenetic abnormalities. Hence, it is important to consider/discuss other diagnostic methods which can utilize peripheral blood (such as high-throughput sequencing technologies) in this context [17]. Mutation analysis based on Sanger sequencing, PCR, and next-generation sequencing (NGS) technologies has been introduced in many centers and is able to detect MDS-related mutations in bone marrow and may be used to advance classification and prognostication of MDS. In recent years, the field of molecular diagnostics has been significantly advanced with the introduction of NGS. There are now multiple commercially available NGS assays, each with a unique method of template preparation, sequencing and imaging and different approaches for the analysis of data [18–20].
Author contributions
Conflict of interest
Acknowledgments This study was supported in part by National Cancer Institute Grant CA-06927 and an appropriation from the Commonwealth of Pennsylvania. The Fox Chase Cancer Center Genomics Facility was used in the course of this work. The study sponsors had no involvement in the study design, collection, analysis and interpretation of data.