PMID- 25831238 OWN - NLM STAT- MEDLINE DCOM- 20160209 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 11 DP - 2015 Apr 20 TI - Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma. PG - 9434-44 AB - The deletion of 12p (del(12p)) has been described as a novel negative prognostic marker in multiple myeloma (MM) and has gained increasing attention in recent years. However, its impact on MM is still controversial. In this study, we comprehensively evaluated the clinical impact of 12p13 deletion using fluorescence in situ hybridization (FISH) on 275 newly diagnosed MM cases treated in a prospective, non-randomized clinical trial (BDH 2008/02). The results showed that deletion of 12p13 was detected in 10.5% of newly diagnosed cases and associated with multiple indicators for high tumor burden including ISS III, BM plasmacytosis larger than 50%, and renal lesion. Moreover, the cases with 12p13 deletion typically had higher incidence of del(17p), IGH translocation and t(4;14). Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy. When adjusted to the established prognostic variables including del(13q), del(17p), t(4;14), amp(1q21), ISS stage and LDH, del(12p13) remained the powerful independent adverse factor for PFS (P = 0.007) and OS (P = 0.032). In addition, del(12p13) combined with high beta2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features. Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM. FAU - Li, Fei AU - Li F AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. AD - Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China. FAU - Xu, Yan AU - Xu Y AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Deng, Ping AU - Deng P AD - Department of Science and Education, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China. FAU - Yang, Ye AU - Yang Y AD - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA. FAU - Sui, Weiwei AU - Sui W AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Jin, Fengyan AU - Jin F AD - Tumor Center, The First Hospital of Jilin University, Changchun 130021, China. FAU - Hao, Mu AU - Hao M AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Li, Zengjun AU - Li Z AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Zang, Meirong AU - Zang M AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Zhou, Dehui AU - Zhou D AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Gu, Zhimin AU - Gu Z AD - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA. FAU - Ru, Kun AU - Ru K AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Wang, Jianxiang AU - Wang J AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Cheng, Tao AU - Cheng T AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. FAU - Qiu, Lugui AU - Qiu L AD - State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. AD - Umbilical Cord Blood Bank of Tianjin, Tianjin 300020, China. LA - eng PT - Clinical Trial PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (Proteasome Inhibitors) RN - 69G8BD63PP (Bortezomib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/pharmacology/*therapeutic use MH - Biomarkers, Tumor/analysis MH - Bortezomib/pharmacology/*therapeutic use MH - *Chromosome Deletion MH - *Chromosomes, Human, Pair 12/ultrastructure MH - Disease-Free Survival MH - Drug Resistance, Neoplasm/*genetics MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Multiple Myeloma/complications/drug therapy/*genetics/mortality MH - Neoplasm Staging MH - Osteolysis/etiology MH - Paraproteinemias/genetics MH - Prognosis MH - Prospective Studies MH - Proteasome Inhibitors/pharmacology/*therapeutic use MH - Translocation, Genetic MH - Tumor Burden PMC - PMC4496228 OTO - NOTNLM OT - 12p13 deletion OT - CD27 gene OT - bortezomib OT - multiple myeloma OT - prognosis COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests. EDAT- 2015/04/02 06:00 MHDA- 2016/02/10 06:00 PMCR- 2015/04/20 CRDT- 2015/04/02 06:00 PHST- 2015/01/09 00:00 [received] PHST- 2015/02/08 00:00 [accepted] PHST- 2015/04/02 06:00 [entrez] PHST- 2015/04/02 06:00 [pubmed] PHST- 2016/02/10 06:00 [medline] PHST- 2015/04/20 00:00 [pmc-release] AID - 3319 [pii] AID - 10.18632/oncotarget.3319 [doi] PST - ppublish SO - Oncotarget. 2015 Apr 20;6(11):9434-44. doi: 10.18632/oncotarget.3319.