Clinical impact of MYC abnormalities in plasma cell myeloma.

Clinically and genomically, plasma cell myeloma (PCM) is a complex disease affecting the elderly population and has often had a poor prognosis. Karyotypic analysis of tumor cells is somewhat limited due to a low proliferative index coupled with a low frequency of tumor cells in clinical samples. Nevertheless, complex karyotypes with a multitude of numerical, balanced and unbalanced structural aberrations have been reported in these tumors. In this study we evaluated the karyotypes obtained in a single institution to identify recurring cytogenetic abnormalities. We constructed evolutionary pathways to differentiate abnormalities present at the beginning of evolution from those that developed later in evolution. We then estimated genetic progression scores and the clinical impact of the cytogenetic abnormalities on survival. In addition, we also evaluated the clinical significance of MYC related abnormalities (translocations and numerical changes) in disease evolution and on survival. Our results indicate that PCM with MYC related abnormalities in general have advanced tumors and adverse outcomes even with low proliferation. Trisomy 8 also contributes to unfavorable outcomes in PCM, this has not been reported previously.