Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups

被引：146

作者：

Bolli, Niccolo ^{[1
,2
,3
]}

Biancon, Giulia ^{[1
]}

Moarii, Matahi ^{[4
]}

Gimondi, Silvia ^{[1
]}

Li, Yilong ^{[3
]}

de Philippis, Chiara ^{[1
,2
]}

Maura, Francesco ^{[1
]}

Sathiaseelan, Vijitha ^{[3
]}

Tai, Yu-Tzu ^{[5
,6
]}

Mudie, Laura ^{[3
]}

O'Meara, Sarah ^{[3
]}

Raine, Keiran ^{[3
]}

Teague, Jon W. ^{[3
]}

Butler, Adam P. ^{[3
]}

Carniti, Cristiana ^{[2
]}

Gerstung, Moritz ^{[7
]}

Bagratuni, Tina ^{[8
]}

Kastritis, Efstathios ^{[8
]}

Dimopoulos, Meletios ^{[8
]}

Corradini, Paolo ^{[1
,2
]}

Anderson, Kenneth C. ^{[5
,6
]}

Moreau, Philippe ^{[9
]}

Minvielle, Stephane ^{[9
,10
]}

Campbell, Peter J. ^{[3
]}

Papaemmanuil, Elli ^{[4
]}

Avet-Loiseau, Herve ^{[11
,12
]}

Munshi, Nikhil C. ^{[5
,6
]}

机构：

[1] Univ Milan, Dept Oncol & Oncohematol, Milan, Italy

[2] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol & Hematol, Milan, Italy

[3] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England

[4] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[5] Harvard Med Sch, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA

[7] European Bioinformat Inst, Computat & Canc Biol, Cambridge, England

[8] Natl & Kapodistrian Univ Athens, Dept Clin Therapeut, Athens, Greece

[9] Univ Hosp Hotel Dieu, Dept Hematol, Nantes, France

[10] Univ Nantes, Univ Angers, CNRS, CRCINA,INSERM, Nantes, France

[11] Inst Univ Canc Toulouse Oncopole, Toulouse, France

[12] Univ Hosp, Toulouse, France

来源：

LEUKEMIA | 2018年 / 32卷 / 12期

基金：

英国惠康基金;

关键词：

COPY NUMBER CHANGES; INTRACLONAL HETEROGENEITY; CLONAL HEMATOPOIESIS; SOMATIC MUTATIONS; GENE; CLASSIFICATION; TRANSLOCATIONS; HYPERDIPLOIDY; T(4/14); REVEALS;

D O I：

10.1038/s41375-018-0037-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication.

引用

页码：2604 / 2616

页数：13

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