Clinical impact of chromothriptic Complex Chromosomal Rearrangements in newly diagnosed multiple myeloma

Abstract

Complex Chromosomal Rearrangements (CCRs) are increasingly being reported as genetic risk factors of clinical significance in cancer owing to their identification using high resolution whole genome profiling technologies. This study employed high resolution CGH + SNP microarrays for whole genome copy number variations (CNV) profiling and identified CCRs in 11/107(10%) newly diagnosed Multiple Myeloma (MM) patients. Six patients exhibited Chromothripsis (CTH) among seven chromosomes that were confirmed with automated CTLPscanner web tool and; five cases displayed chromoplexy (CPL) which involved multiple chromosomes. Presence of chromothripsis in chromosome 17 in three out of six patients indicate a link between TP53 aberrations and incidence of CTH. Multivariable Cox regression model demonstrated a significant association of CTH with poor PFS (HR = 3.09, p = 0.010) and OS (HR = 3.31, p = 0.024) which suggests that CTH is an additional independent prognostic marker in multiple myeloma. Addition of CTH in risk stratification models in clinical setting in multiple myeloma may help in upfront identification of high risk patients for suitable customized therapy.