title: Copy number variations could predict the outcome of bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
abstract: We performed single nucleotide polymorphism (SNP) array analysis of 35 newly diagnosed symptomatic multiple myeloma (MM) patients who received bortezomib-melphalan-prednisone (VMP) to identify collaborating genetic events that could predict the outcome of treatment. A total of 340 copy number variations (CNVs) were identified, with the most frequently identified CNVs being gains on 1q, 19p, 9q, 3q, 9p, 15q, 19q, 5q, 11q, 5p, and 7q and losses on 1p, X, 13q, 14q, and 6q. The number and proportion of detected abnormalities by SNP array were associated with presence of cytogenetic abnormalities and complex karyotype. Moreover, increasing genomic complexity as ascertained by SNP arrays correlated with outcome of the VMP treatment. The frequency of CNVs was significantly different according to achievement of very good partial response (VGPR) to VMP treatment (<VGPR vs. ≥VGPR, median 11.7 vs. 7.7, respectively, P = 0.032) or occurrence of progressive disease (PD) after VMP treatment (progression vs. nonprogression, median 11.6 and 6.5, respectively, P = 0.011). The proportion of CNV length was also significantly higher in patients who did not achieve VGPR compared with those with ≥VGPR (median 31.9 vs. 19.6%, respectively, P = 0.004) and also higher in patients with PD compared with those without it (median 31.9 vs. 15.8%, respectively, P = 0.005). The patients who did not achieve VGPR tended to have deletion of 1p (P = 0.011) and gain of 3q (P = 0.05). Occurrence of PD was associated with complex karyotype (P = 0.020) and gain of 3q (P = 0.022). Our data show that the occurrence of CNVs correlates with clinical outcomes to first-line VMP treatment.
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.forename: Shin Hyo
authors.initials: SH
authors.lastname: Lee
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002877:Chromosomes, Human / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone