Complex Genomic Rearrangements Involving :: Gene Fusion in an Individual with Myeloid Neoplasm.

:: gene fusion is a rare recurrent genomic rearrangement associated with hematologic malignancies, and frequently occurs with additional anomalies. Due to the opposite chromosome orientations of the and genes, an oncogenic in-frame :: gene fusion cannot be formed by a simple translocation. The molecular mechanism of the :: fusion and the significance of co-occurring anomalies are not fully understood. We characterized genomic alterations in an individual with :: gene-fusion-positive myeloid neoplasm using various genomic technologies. Our findings uncovered a molecular mechanism of the :: fusion, in which a paracentric inversion within the short arm of chromosome 12 (12p) and a translocation between the long arm of a chromosome 9 and the 12p with the inversion were involved. In addition, we detected multiple additional anomalies in the individual, and our findings suggested that the :: fusion occurred as a secondary event in a subset of cells with the additional anomalies. We speculate that the additional anomalies may predispose to further pathogenic changes, including :: fusion, leading to neoplastic transformation.