[Recent advancements in molecular cytogenetics for hematological malignancies: identification of novel PVT1 fusion genes].

Specific chromosomal abnormalities are of diagnostic and prognostic relevance as well as providing clues for the identification of causative genes in patients with hematological malignancies. Genomic array (GA) is a powerful tool for identifying both microdeletion and precise DNA breakpoints in the genes of interest. For example, GA was able to detect CDKN2A and CDKN2B deletions in a small region only 69kb in size at 9p21 that were frequently found in patients with double-hit lymphoma. Using GA combined with spectral karyotyping, fluorescence in situ hybridization, and RT-PCR, we have identified a novel PVT1 rearrangement at 8q24 which were partnered with NBEA and WWOX in multiple myeloma (MM). In patients with MM, NBEA and WWOX are frequently involved in chromosomal deletion at 13q14 and 16q23, respectively. In acute myeloid leukemia, novel fusion RNAs, PVT1-NSMCE2 and CCDC26-NSMCE2, were identified in association with marker chromosomes and double minute chromosomes derived from chromosome 8 showing 8q24 amplicons. Chromothripsis is a possible cytogenetic mechanism of generating PVT1-NSMCE2 and CCDC26-NSMCE2. As PVT1 and CCDC26 are long intergenic non-coding RNAs (lincRNAs), our study suggests that the fusion genes involving lincRNAs potentially play as-yet-unknown oncogenic functional roles. Advancements in molecular cytogenetic techniques along with next generation sequencing will facilitate the understanding of tumorigenesis in hematological malignancies.