Optical Genome Mapping Helps to Identify Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review.

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible rearrangement and a reflex JAK2 breakapart probe indicated rearrangement, most likely partnered with . Optical genome mapping (OGM) analysis confirmed derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as , and were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with rearrangement reported in the literature. In conclusion, a suspected t(9;22)/ rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements.