Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence

被引：44

作者：

Misund, Kristine ^{[1
,2
]}

Hofste Op Bruinink, Davine ^{[3
]}

Coward, Eivind ^{[1
,4
,5
]}

Hoogenboezem, Remco M. ^{[3
]}

Rustad, Even Holth ^{[1
,6
]}

Sanders, Mathijs A.

Rye, Morten ^{[1
,4
,7
,8
]}

Sponaas, Anne-Marit ^{[1
]}

van der Holt, Bronno ^{[9
]}

Zweegman, Sonja ^{[10
]}

Hovig, Eivind ^{[11
,12
]}

Meza-Zepeda, Leonardo A. ^{[11
,13
]}

Sundan, Anders ^{[1
]}

Myklebost, Ola ^{[11
,14
]}

Sonneveld, Pieter ^{[3
]}

Waage, Anders ^{[1
,2
]}

机构：

[1] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway

[2] St Olavs Hosp, Dept Hematol, Trondheim, Norway

[3] Erasmus MC Canc Inst, Dept Hematol, Rotterdam, Netherlands

[4] Norwegian Univ Sci & Technol, Bioinformat Core Facil BioCore, Trondheim, Norway

[5] Norwegian Univ Sci & Technol, KG Jebsen Ctr Genet Epidemiol, Trondheim, Norway

[6] Oslo Univ Hosp, Inst Canc Res, Oslo, Norway

[7] St Olavs Hosp, Clin Lab Med, Trondheim, Norway

[8] St Olavs Hosp, Surg Clin, Trondheim, Norway

[9] Erasmus MC Canc Inst, Dept Hematol, HOVON Data Ctr, Rotterdam, Netherlands

[10] Amsterdam UMC, Dept Hematol, Amsterdam, Netherlands

[11] Oslo Univ Hosp, Inst Canc Res, Dept Tumour Biol, Oslo, Norway

[12] Univ Oslo, Dept Informat, Ctr Bioinformat, Oslo, Norway

[13] Oslo Univ Hosp, Dept Core Facil, Genom Core Facil, Oslo, Norway

[14] Univ Bergen, Dept Clin Sci, Bergen, Norway

来源：

LEUKEMIA | 2022年 / 36卷 / 07期

关键词：

CANCER-TESTIS ANTIGENS; MOLECULAR CLASSIFICATION; COPY NUMBER; LENALIDOMIDE; EXPRESSION; PREDNISONE; MELPHALAN; PROFILES; REVEALS; COMPLEX;

D O I：

10.1038/s41375-022-01597-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We investigated genomic and transcriptomic changes in paired tumor samples of 29 in-house multiple myeloma (MM) patients and 28 patients from the MMRF CoMMpass study before and after treatment. A change in clonal composition was found in 46/57 (82%) of patients, and single-nucleotide variants (SNVs) increased from median 67 to 86. The highest increase in prevalence of genetic aberrations was found in RAS genes (60% to 72%), amp1q21 (18% to 35%), and TP53 (9% to 18%). The SBS-MM1 mutation signature was detected both in patients receiving high and low dose melphalan. A total of 2589 genes were differentially expressed between early and late samples (FDR < 0.05). Gene set enrichment analysis (GSEA) showed increased expression of E2F, MYC, and glycolysis pathways and a decreased expression in TNF-NFkB and TGFbeta pathways in late compared to early stage. Single sample GSEA (ssGSEA) scores of differentially expressed pathways revealed that these changes were most evident in end-stage disease. Increased expression of several potentially targetable genes was found at late disease stages, including cancer-testis antigens, XPO1 and ABC transporters. Our study demonstrates a transcriptomic convergence of pathways supporting increased proliferation and metabolism during disease progression in MM.

引用

页码：1887 / 1897

页数：11

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