Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients

被引：6

作者：

Macauda, Angelica ^{[1
,2
]}

Piredda, Chiara ^{[2
]}

Clay-Gilmour, Alyssa, I ^{[3
]}

Sainz, Juan ^{[4
,5
]}

Buda, Gabriele ^{[6
]}

Markiewicz, Miroslaw ^{[7
]}

Barington, Torben ^{[8
]}

Ziv, Elad ^{[9
]}

Hildebrandt, Michelle A. T. ^{[10
]}

Belachew, Alem A. ^{[10
]}

Varkonyi, Judit ^{[11
]}

Prejzner, Witold ^{[12
]}

Druzd-Sitek, Agnieszka ^{[13
]}

Spinelli, John ^{[14
,15
]}

Andersen, Niels Frost ^{[16
]}

Hofmann, Jonathan N. ^{[17
]}

Dudzinski, Marek ^{[18
]}

Martinez-Lopez, Joaquin ^{[19
]}

Iskierka-Jazdzewska, Elzbieta ^{[20
]}

Milne, Roger L. ^{[21
,22
,23
]}

Mazur, Grzegorz ^{[24
]}

Giles, Graham G. ^{[21
,22
,23
]}

Ebbesen, Lene Hyldahl ^{[16
]}

Rymko, Marcin ^{[25
]}

Jamroziak, Krzysztof ^{[26
]}

Subocz, Edyta ^{[27
]}

Reis, Rui Manuel ^{[28
,29
]}

Garcia-Sanz, Ramon ^{[30
]}

Suska, Anna ^{[31
]}

Haastrup, Eva Kannik ^{[32
]}

Zawirska, Daria ^{[33
]}

Grzasko, Norbert ^{[34
,35
]}

Vangsted, Annette Juul ^{[32
]}

Dumontet, Charles ^{[36
]}

Kruszewski, Marcin ^{[37
]}

Dutka, Magdalena ^{[12
]}

Camp, Nicola J. ^{[38
]}

Waller, Rosalie G. ^{[38
]}

Tomczak, Waldemar ^{[39
]}

Pelosini, Matteo ^{[6
]}

Razny, Malgorzata ^{[40
]}

Marques, Herlander ^{[29
]}

Abildgaard, Niels ^{[41
]}

Watek, Marzena ^{[42
]}

Jurczyszyn, Artur ^{[31
]}

Brown, Elizabeth E. ^{[43
]}

Berndt, Sonja ^{[17
]}

Butrym, Aleksandra ^{[24
]}

Vachon, Celine M. ^{[44
,45
]}

Norman, Aaron D. ^{[44
,45
]}

机构：

[1] German Canc Res Ctr, Genom Epidemiol Grp, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[2] Univ Pisa, Dept Biol, Pisa, Italy

[3] Univ South Carolina, Dept Epidemiol & Biostat, Arnold Sch Publ Hlth, Columbia, SC 29208 USA

[4] Univ Granada, GENYO Ctr Genom & Oncol Res Pfizer, Genom Oncol Area, Andalusian Reg Govt, Granada, Spain

[5] Virgen de las Nieves Univ Hosp, Hematol Dept, Granada, Spain

[6] Univ Pisa, Sect Hematol, Clin & Expt Med, Pisa, Italy

[7] SPSKM Hosp, Dept Hematol & Bone Marrow Transplantat, Katowice, Poland

[8] Odense Univ Hosp, Dept Clin Immunol, Odense, Denmark

[9] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Inst Human Genet,Helen Diller Family Comprehens C, San Francisco, CA 94143 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA

[11] Semmelweis Univ, Dept Internal Med 3, Budapest, Hungary

[12] Med Univ Gdansk, Dept Hematol & Transplantat, Gdansk, Poland

[13] Maria Sklodowska Curie Natl Res Inst Oncol, Dept Lymphoid Malignacies, Warsaw, Poland

[14] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada

[15] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada

[16] Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark

[17] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[18] Univ Rzeszow, Coll Med Sci, Inst Med Sci, Dept Hematol, Rzeszow, Poland

[19] Univ Complutense Madrid, CIBERONC, CNIO, Hosp 12 Octubre, Madrid, Spain

[20] Copernicus Mem Hosp, Dept Haematol, Lodz, Poland

[21] Canc Council Victoria, Canc Epidemiol Div, Victoria, Australia

[22] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Victoria, Australia

[23] Monash Univ, Sch Clin Sci, Precis Med, Monash Hlth, Clayton, Vic, Australia

[24] Wroclaw Med Univ, Dept Internal & Occupat Dis, Hypertens & Clin Oncol, Wroclaw, Poland

[25] N Copernicus Town Hosp, Dept Hematol, Torun, Poland

[26] Inst Hematol & Transfus Med, Dept Hematol, Warsaw, Poland

[27] Mil Inst Med, Dept Haematol, Warsaw, Poland

[28] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal

[29] Mol Oncol Res Ctr, Sao Paulo, Brazil

[30] Univ Hosp Salamanca, Dept Hematol, IBSAL, Salamanca, Spain

[31] Jagiellonian Univ, Dept Hematol, Med Coll, Krakow, Poland

[32] Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark

[33] Univ Hosp Cracow, Dept Hematol, Krakow, Poland

[34] Med Univ Lublin, Dept Expt Hematooncol, Lublin, Poland

[35] St Johns Canc Ctr, Dept Hematol, Lublin, Poland

[36] Hosp Civils Lyon, Canc Res Ctr Lyon, Lyon, France

[37] Univ Hosp Bydgoszcz, Dept Hematol, Bydgoszcz, Poland

[38] Univ Utah, Salt Lake City, UT USA

[39] Med Univ Lublin, Lublin, Poland

[40] Rydygier Specialist Hosp, Dept Hematol, Krakow, Poland

[41] Odense Univ Hosp, Dept Hematol, Odense, Denmark

[42] Holycross Canc Ctr, Hematol Clin, Kielce, Poland

[43] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[44] Mayo Clin, Mayo Clin Comprehens Canc Ctr, Genet Epidemiol & Risk Assessment Program, Rochester, MN USA

[45] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA

来源：

INTERNATIONAL JOURNAL OF CANCER | 2021年 / 149卷 / 02期

基金：

加拿大健康研究院; 英国医学研究理事会;

关键词：

eQTL; genetic polymorphisms; multiple myeloma; overall survival; progression‐ free survival; GENOME-WIDE ASSOCIATION; REGULATORS; SIGNATURES; VARIANTS; GENETICS; THERAPY; MODEL; POWER;

D O I：

10.1002/ijc.33547

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10(-7) either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.

引用

页码：327 / 336

页数：10

共 39 条

[1] Annotation of functional variation in personal genomes using RegulomeDB [J].

Boyle, Alan P. ;

Hong, Eurie L. ;

Hariharan, Manoj ;

Cheng, Yong ;

Schaub, Marc A. ;

Kasowski, Maya ;

Karczewski, Konrad J. ;

Park, Julie ;

Hitz, Benjamin C. ;

Weng, Shuai ;

Cherry, J. Michael ;

Snyder, Michael .

GENOME RESEARCH, 2012, 22 (09) :1790-1797

[2] Genetic polymorphisms in genes of class switch recombination and multiple myeloma risk and survival: an IMMEnSE study [J].

Campa, Daniele ;

Martino, Alessandro ;

Macauda, Angelica ;

Dudzinski, Marek ;

Suska, Anna ;

Druzd-Sitek, Agnieszka ;

Raab, Marc-Steffen ;

Moreno, Victor ;

Huhn, Stefanie ;

Butrym, Aleksandra ;

Sainz, Juan ;

Szombath, Gergely ;

Rymko, Marcin ;

Marques, Herlander ;

Lesueur, Fabienne ;

Vangsted, Annette Juul ;

Vogel, Ulla ;

Kruszewski, Marcin ;

Subocz, Edyta ;

Buda, Gabriele ;

Iskierka-Jazdzewska, Elzbieta ;

Rios, Rafael ;

Merz, Maximilian ;

Schoettker, Ben ;

Mazur, Grzegorz ;

Perrial, Emeline ;

Martinez-Lopez, Joaquin ;

Butterbach, Katja ;

Garcia Sanz, Ramon ;

Goldschmidt, Hartmut ;

Brenner, Hermann ;

Jamroziak, Krzysztof ;

Reis, Rui Manuel ;

Kadar, Katalin ;

Dumontet, Charles ;

Watek, Marzena ;

Haastrup, Eva Kannik ;

Helbig, Grzegorz ;

Jurczyszyn, Artur ;

Jerez, Andres ;

Varkonyi, Judit ;

Barington, Torben ;

Grzasko, Norbert ;

Zaucha, Jan Maciej ;

Andersen, Vibeke ;

Zawirska, Daria ;

Canzian, Federico .

LEUKEMIA & LYMPHOMA, 2019, 60 (07) :1803-1811

[3] Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients:: A study of the intergroupe francophone du myelome [J].

Decaux, Olivier ;

Lode, Laurence ;

Magrangeas, Florence ;

Charbonnel, Catherine ;

Gouraud, Wilfried ;

Jezequel, Pascal ;

Attal, Michel ;

Harousseau, Jean-Luc ;

Moreau, Philippe ;

Bataille, Regis ;

Campion, Loic ;

Avert-Loiseau, Herve ;

Minvielle, Stephane .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (29) :4798-4805

[4] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[5] A common genetic variant in 19q13.3 is associated with outcome of multiple myeloma patients treated with Total Therapy 2 and 3 [J].

Erickson, Stephen W. ;

Stephens, Owen W. ;

Chavan, Shweta S. ;

Epstein, Joshua ;

Barlogie, Bart ;

Heuck, Christoph J. ;

Vangsted, Annette J. .

BRITISH JOURNAL OF HAEMATOLOGY, 2016, 174 (06) :991-993

[6] Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles [J].

Fairfax, Benjamin P. ;

Makino, Seiko ;

Radhakrishnan, Jayachandran ;

Plant, Katharine ;

Leslie, Stephen ;

Dilthey, Alexander ;

Ellis, Peter ;

Langford, Cordelia ;

Vannberg, Fredrik O. ;

Knight, Julian C. .

NATURE GENETICS, 2012, 44 (05) :502-+

[7] Pharmacogenetic study of the impact of ABCB1 single-nucleotide polymorphisms on lenalidomide treatment outcomes in patients with multiple myeloma: results from a phase IV observational study and subsequent phase II clinical trial [J].

Falk, Ingrid Jakobsen ;

Lund, Johan ;

Green, Henrik ;

Gruber, Astrid ;

Alici, Evren ;

Lauri, Birgitta ;

Blimark, Cecilie ;

Mellqvist, Ulf-Henrik ;

Swedin, Agneta ;

Forsberg, Karin ;

Carlsson, Conny ;

Hardling, Mats ;

Ahlberg, Lucia ;

Lotfi, Kourosh ;

Nahi, Hareth .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2018, 81 (01) :183-193

[8] A genome-wide study of Hardy-Weinberg equilibrium with next generation sequence data [J].

Graffelman, Jan ;

Jain, Deepti ;

Weir, Bruce .

HUMAN GENETICS, 2017, 136 (06) :727-741

[9] Gene expression risk signatures maintain prognostic power in multiple myeloma despite microarray probe set translation [J].

Hermansen, N. E. U. ;

Borup, R. ;

Andersen, M. K. ;

Vangsted, A. J. ;

Clausen, N. T. ;

Kristensen, D. L. ;

Nielsen, F. C. ;

Gimsing, P. .

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 2016, 38 (03) :298-307

[10] Five gene probes carry most of the discriminatory power of the 70-gene risk model in multiple myeloma [J].

Heuck, C. J. ;

Qu, P. ;

van Rhee, F. ;

Waheed, S. ;

Usmani, S. Z. ;

Epstein, J. ;

Zhang, Q. ;

Edmondson, R. ;

Hoering, A. ;

Crowley, J. ;

Barlogie, B. .

LEUKEMIA, 2014, 28 (12) :2410-2413

← 1 2 3 4 →