Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

PLoS Genetics

Volumn 13, Issue 11, 2017, Pages

  Manojlovic, Zarko ^a,b   Christofferson, Austin ^b   Liang, Winnie S ^b   Aldrich, Jessica ^b   Washington, Megan ^b   Wong, Shukmei ^b   Rohrer, Daniel ^c   Jewell, Scott ^c   Kittles, Rick A ^d   Derome, Mary ^e   Auclair, Daniel ^e   Craig, David Wesley ^a   Keats, Jonathan ^b   Carpten, John D ^a,b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

^c VAN ANDEL RESEARCH INSTITUTE   (United States)

^d UNIVERSITY OF ARIZONA   (United States)

^e Multiple Myeloma Research Foundation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AFRICAN; ANCESTRY GROUP; ARTICLE; AUTS2 GENE; BCL7A GENE; BRWD3 GENE; ETHNIC DIFFERENCE; EUROPEAN; EXOME; GENE; GENE FUNCTION; GENE MUTATION; GENE TRANSLOCATION; HUMAN; IRF4 GENE; MAJOR CLINICAL STUDY; MULTIPLE MYELOMA; MUTATION RATE; RNA SEQUENCE; SELF REPORT; SOMATIC MUTATION; TP53 GENE; ADULT; BLACK PERSON; CAUCASIAN; FEMALE; GENETICS; GENOTYPE; HIGH THROUGHPUT SEQUENCING; MALE; MIDDLE AGED; MUTATION; PATHOLOGY;

ACTIN BINDING PROTEIN; AUTS2 PROTEIN, HUMAN; BCL7A PROTEIN, HUMAN; BRWD3 PROTEIN, HUMAN; INTERFERON REGULATORY FACTOR; INTERFERON REGULATORY FACTOR-4; ONCOPROTEIN; PROTEIN; PROTEIN P53; TP53 PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ADULT; AFRICAN CONTINENTAL ANCESTRY GROUP; CONTINENTAL POPULATION GROUPS; EUROPEAN CONTINENTAL ANCESTRY GROUP; EXOME; FEMALE; GENOTYPE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; INTERFERON REGULATORY FACTORS; MALE; MICROFILAMENT PROTEINS; MIDDLE AGED; MULTIPLE MYELOMA; MUTATION; MUTATION RATE; ONCOGENE PROTEINS; PROTEINS; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 85036614434     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1007087     Document Type: Article

References (57)

1. Greenberg AJ, Vachon CM, Rajkumar SV, Disparities in the prevalence, pathogenesis and progression of monoclonal gammopathy of undetermined significance and multiple myeloma between blacks and whites. Leukemia. 2012;26(4):609–14. doi: 10.1038/leu.2011.368 22193966; PubMed Central PMCID: PMCPMC3629947.
2. Hideshima T, Bergsagel PL, Kuehl WM, Anderson KC, Advances in biology of multiple myeloma: clinical applications. Blood. 2004;104(3):607–18. doi: 10.1182/blood-2004-01-0037 15090448.
3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ, Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49. doi: 10.3322/caac.20006 19474385.
4. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412–7. doi: 10.1182/blood-2008-12-194241 19179464; PubMed Central PMCID: PMCPMC2689042.
5. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM, A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22):5418–22. doi: 10.1182/blood-2008-12-195008 19234139; PubMed Central PMCID: PMCPMC2689043.
6. Benjamin M, Reddy S, Brawley OW, Myeloma and race: a review of the literature. Cancer Metastasis Rev. 2003;22(1):87–93. 12716040.
7. Becker N, Epidemiology of multiple myeloma. Recent Results Cancer Res. 2011;183:25–35. doi: 10.1007/978-3-540-85772-3_2 21509679.
8. Landgren O, Graubard BI, Katzmann JA, Kyle RA, Ahmadizadeh I, Clark R, et al. Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12,482 persons from the National Health and Nutritional Examination Survey. Leukemia. 2014;28(7):1537–42. doi: 10.1038/leu.2014.34 24441287; PubMed Central PMCID: PMCPMC4090286.
9. StatBite. StatBite: Multiple myeloma and African Americans: higher incidence but fewer autologous stem cell transplants. J Natl Cancer Inst. 2009;101(23):1610. doi: 10.1093/jnci/djp435 19910557.
10. Waxman AJ, Mink PJ, Devesa SS, Anderson WF, Weiss BM, Kristinsson SY, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood. 2010;116(25):5501–6. doi: 10.1182/blood-2010-07-298760 20823456; PubMed Central PMCID: PMCPMC3031400.
11. Srivastava G, Rana V, Lacy MQ, Buadi FK, Hayman SR, Dispenzieri A, et al. Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma. Leukemia. 2013;27(10):2062–6. doi: 10.1038/leu.2013.143 23648667; PubMed Central PMCID: PMCPMC3795989.
12. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467–72. doi: 10.1038/nature09837 21430775; PubMed Central PMCID: PMCPMC3560292.
13. Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25(1):91–101. doi: 10.1016/j.ccr.2013.12.015 24434212; PubMed Central PMCID: PMCPMC4241387.
14. Baker A, Braggio E, Jacobus S, Jung S, Larson D, Therneau T, et al. Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach. Blood. 2013;121(16):3147–52. doi: 10.1182/blood-2012-07-443606 23422747; PubMed Central PMCID: PMCPMC3630830.
15. Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, Zhivotovsky LA, et al. Genetic structure of human populations. Science. 2002;298(5602):2381–5. doi: 10.1126/science.1078311 12493913.
16. Kumar R, Seibold MA, Aldrich MC, Williams LK, Reiner AP, Colangelo L, et al. Genetic ancestry in lung-function predictions. N Engl J Med. 2010;363(4):321–30. doi: 10.1056/NEJMoa0907897 20647190; PubMed Central PMCID: PMCPMC2922981.
17. Yang JJ, Cheng C, Devidas M, Cao X, Fan Y, Campana D, et al. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nat Genet. 2011;43(3):237–41. doi: 10.1038/ng.763 21297632; PubMed Central PMCID: PMCPMC3104508.
18. Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. doi: 10.1038/nature15393 26432245; PubMed Central PMCID: PMCPMC4750478.
19. Pritchard JK, Stephens M, Donnelly P, Inference of population structure using multilocus genotype data. Genetics. 2000;155(2):945–59. 10835412; PubMed Central PMCID: PMCPMC1461096.
20. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8. doi: 10.1038/nature12213 23770567; PubMed Central PMCID: PMCPMC3919509.
21. Egan JB, Shi CX, Tembe W, Christoforides A, Kurdoglu A, Sinari S, et al. Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood. 2012;120(5):1060–6. doi: 10.1182/blood-2012-01-405977 22529291; PubMed Central PMCID: PMCPMC3412329.
22. Mermel CH, Schumacher SE, Hill B, Meyerson ML, Beroukhim R, Getz G, GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 2011;12(4):R41. doi: 10.1186/gb-2011-12-4-r41 21527027; PubMed Central PMCID: PMCPMC3218867.
23. Shaughnessy JD, Jr.Zhan F, Burington BE, Huang Y, Colla S, Hanamura I, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276–84. doi: 10.1182/blood-2006-07-038430 17105813.
24. Bergsagel PL, Kuehl WM, Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol. 2005;23(26):6333–8. doi: 10.1200/JCO.2005.05.021 16155016.
25. Chng WJ, Kumar S, Vanwier S, Ahmann G, Price-Troska T, Henderson K, et al. Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling. Cancer Res. 2007;67(7):2982–9. doi: 10.1158/0008-5472.CAN-06-4046 17409404.
26. Walker BA, Boyle EM, Wardell CP, Murison A, Begum DB, Dahir NM, et al. Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma. J Clin Oncol. 2015;33(33):3911–20. doi: 10.1200/JCO.2014.59.1503 26282654.
27. Andrulis M, Lehners N, Capper D, Penzel R, Heining C, Huellein J, et al. Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov. 2013;3(8):862–9. Epub 2013/04/25. doi: 10.1158/2159-8290.CD-13-0014 23612012.
28. O'Donnell E, Raje NS, Targeting BRAF in multiple myeloma. Cancer Discov. 2013;3(8):840–2. Epub 2013/08/10. doi: 10.1158/2159-8290.CD-13-0297 23928771.
29. Rustad EH, Dai HY, Hov H, Coward E, Beisvag V, Myklebost O, et al. BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis. Blood Cancer J. 2015;5:e299. Epub 2015/03/21. doi: 10.1038/bcj.2015.24 25794135; PubMed Central PMCID: PMCPMC4382665.
30. Zani VJ, Asou N, Jadayel D, Heward JM, Shipley J, Nacheva E, et al. Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon. Blood. 1996;87(8):3124–34. 8605326.
31. Muller P, Kuttenkeuler D, Gesellchen V, Zeidler MP, Boutros M, Identification of JAK/STAT signalling components by genome-wide RNA interference. Nature. 2005;436(7052):871–5. doi: 10.1038/nature03869 16094372.
32. Kalla C, Nentwich H, Schlotter M, Mertens D, Wildenberger K, Dohner H, et al. Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes. Genes Chromosomes Cancer. 2005;42(2):128–43. doi: 10.1002/gcc.20131 15543602.
33. Denk D, Nebral K, Bradtke J, Pass G, Moricke A, Attarbaschi A, et al. PAX5-AUTS2: a recurrent fusion gene in childhood B-cell precursor acute lymphoblastic leukemia. Leuk Res. 2012;36(8):e178–81. Epub 2012/05/15. doi: 10.1016/j.leukres.2012.04.015 22578776; PubMed Central PMCID: PMCPMC3389344.
34. Weinhold N, Ashby C, Rasche L, Chavan SS, Stein C, Stephens OW, et al. Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood. 2016;128(13):1735–44. doi: 10.1182/blood-2016-06-723007 27516441.
35. Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, et al. Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma. Nat Genet. 1997;17(2):226–30. doi: 10.1038/ng1097-226 9326949.
36. Shaffer AL, Emre NC, Lamy L, Ngo VN, Wright G, Xiao W, et al. IRF4 addiction in multiple myeloma. Nature. 2008;454(7201):226–31. doi: 10.1038/nature07064 18568025; PubMed Central PMCID: PMCPMC2542904.
37. Fionda C, Abruzzese MP, Zingoni A, Cecere F, Vulpis E, Peruzzi G, et al. The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma. Oncotarget. 2015;6(27):23609–30. doi: 10.18632/oncotarget.4603 26269456; PubMed Central PMCID: PMCPMC4695140.
38. Lopez-Girona A, Heintel D, Zhang LH, Mendy D, Gaidarova S, Brady H, et al. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol. 2011;154(3):325–36. doi: 10.1111/j.1365-2141.2011.08689.x 21707574.
39. Li H, Durbin R, Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754–60. doi: 10.1093/bioinformatics/btp324 19451168; PubMed Central PMCID: PMCPMC2705234.
40. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25(16):2078–9. doi: 10.1093/bioinformatics/btp352 19505943; PubMed Central PMCID: PMCPMC2723002.
41. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297–303. doi: 10.1101/gr.107524.110 20644199; PubMed Central PMCID: PMCPMC2928508.
42. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43(5):491–8. doi: 10.1038/ng.806 21478889; PubMed Central PMCID: PMCPMC3083463.
43. Li H, A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011;27(21):2987–93. doi: 10.1093/bioinformatics/btr509 21903627; PubMed Central PMCID: PMCPMC3198575.
44. Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31(3):213–9. doi: 10.1038/nbt.2514 23396013; PubMed Central PMCID: PMCPMC3833702.
45. Saunders CT, Wong WS, Swamy S, Becq J, Murray LJ, Cheetham RK, Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics. 2012;28(14):1811–7. doi: 10.1093/bioinformatics/bts271 22581179.
46. Christoforides A, Carpten JD, Weiss GJ, Demeure MJ, Von Hoff DD, Craig DW, Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs. BMC Genomics. 2013;14:302. doi: 10.1186/1471-2164-14-302 23642077; PubMed Central PMCID: PMCPMC3751438.
47. Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115–21. doi: 10.1038/nmeth.3252 25633503; PubMed Central PMCID: PMCPMC4509590.
48. Cingolani P, Platts A, Wang le L, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 2012;6(2):80–92. doi: 10.4161/fly.19695 22728672; PubMed Central PMCID: PMCPMC3679285.
49. Patro R, Mount SM, Kingsford C, Sailfish enables alignment-free isoform quantification from RNA-seq reads using lightweight algorithms. Nat Biotechnol. 2014;32(5):462–4. doi: 10.1038/nbt.2862 24752080; PubMed Central PMCID: PMCPMC4077321.
50. Kosoy R, Nassir R, Tian C, White PA, Butler LM, Silva G, et al. Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America. Hum Mutat. 2009;30(1):69–78. doi: 10.1002/humu.20822 18683858; PubMed Central PMCID: PMCPMC3073397.
51. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D, Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38(8):904–9. doi: 10.1038/ng1847 16862161.
52. Tandon A, Patterson N, Reich D, Ancestry informative marker panels for African Americans based on subsets of commercially available SNP arrays. Genet Epidemiol. 2011;35(1):80–3. doi: 10.1002/gepi.20550 21181899; PubMed Central PMCID: PMCPMC4386999.
53. Rosenberg NA, Li LM, Ward R, Pritchard JK, Informativeness of genetic markers for inference of ancestry. Am J Hum Genet. 2003;73(6):1402–22. doi: 10.1086/380416 14631557; PubMed Central PMCID: PMCPMC1180403.
54. Patterson N, Price AL, Reich D, Population structure and eigenanalysis. PLoS Genet. 2006;2(12):e190. doi: 10.1371/journal.pgen.0020190 17194218; PubMed Central PMCID: PMCPMC1713260.
55. Lischer HE, Excoffier L, PGDSpider: an automated data conversion tool for connecting population genetics and genomics programs. Bioinformatics. 2012;28(2):298–9. doi: 10.1093/bioinformatics/btr642 22110245.
56. Agresti A, A survey of models for repeated ordered categorical response data. Stat Med. 1989;8(10):1209–24. 2814070.
57. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I, Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001;125(1–2):279–84. 11682119.