Chromosome 13 Abnormalities

Approximately 50 % of patients diagnosed with multiple myeloma (MM) have interstitial deletions or monosomy of Chromosome 13. Chromosome 13 abnormalities (13) are associated with a significant reduction in overall survival and resistance to traditional and high-dose therapy regimens. A reported region of minimal deletion on chromosome 13 contains multiple potential genes for investigation, including retinoblastoma (Rb). Rb is a critical regulator of cell cycle progression which suggests it may be the most likely candidate for tumor progression in myeloma. Additionally, two microRNA clusters, miR 15a and 16-1 as well as miR17-92, have been identified on chromosome 13q. MicroRNA (miRs) are a class of small, noncoding RNAs typically between 21 to 23 nucleotides in length that negatively regulate gene expression through degradation of mRNA or inhibition of translation through homologous base pairing. In vitro experiments have identified BCL-2 as a target for miRs 15a and 16-1. Further, miR cluster 17-92 has been reported as myc-responsive with E2F1 and AIB-1 reported as targets. Our laboratory is interested in the possible contributions towards disease progression in myeloma as a consequence of loss of either Rb or miRs on chromosome 13.