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Cited by 10Multiple Myeloma Research and TreatmentsCancer Genomics and DiagnosticsLymphoma Diagnosis and Treatment

Initial whole-genome sequencing of plasma cell neoplasms in first responders and recovery workers exposed to the World Trade Center attack of September 11, 2001

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Maura, Francesco, Diamond, Benjamin, Maclachlan, Kylee H., Derkach, Andriy, Yellapantula, Venkata D., Rustad, Even H., Hultcrantz, Malin, Shah, Urvi A. +17 more·2021·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-20-2245PMC PMC8026670

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Abstract

Purpose: The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole-genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. Experimental Design: We performed WGS of nine CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. Results: No significant differences were observed in comparing the post-WTC driver and mutational signature landscapes with 110 previously published WGSs from 56 patients with multiple myeloma and the CoMMpass WGS cohort (n = 752). Leveraging constant activity of the single-base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. Conclusions: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.

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Crossref · 10.1158/1078-0432.ccr-20-2245

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  • Initial development of HY occurs at a very early age, in the 2nd and 3rd decade of life, with acquisition of additional trisomies and aneuploidies in subsequent decades.

    “Different independent studies have indicated initial development of HY at a very early age, in 2nd and 3rd decade of life with acquisition of additional trisomies and aneuploidies in subsequent decade.9,10,12,13,15”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [10]

    The Results section, “Timing the initiation of plasma cell dyscrasias in WTC-exposed patients” (page unavailable), says a cancer-initiating event can occur in the second or third decade of life and reports chromosomal gains timed in WTC-exposed patients. It does not establish that hyperdiploidy (HY) specifically begins at that age or that additional trisomies and aneuploidies accumulate over subsequent decades. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • SMM that progresses to multiple myeloma has a time of initiation of approximately 30 to 40 years.

    “This has been recently supported by several papers, where using molecular mathematical modeling, it has been shown that SMM that progresses to MM has a time of initiation of approximately 30 to 40 years.9,10,12,13,1515”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [10]

    The Results section (“Timing the initiation of plasma cell dyscrasias in WTC-exposed patients”; page not provided) says a cancer-initiating event can occur 30–40 years before clinical diagnosis. It does not establish that interval specifically for SMM that progresses to multiple myeloma; the paper’s timed SMM case is described as having a clone before the WTC attack, not as having progressed to myeloma. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • All cases of multiple myeloma are preceded by precursor conditions such as smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, often decades before diagnosis.

    “MM is well-described to be universally preceded by precursor states, often decades before it is even diagnosed.”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [10]

  • A significant fraction of SMM has already transformed into MM.

    “This temporal similarity between progressive SMM and MM further strengthens the hypothesis that a significant fraction of SMM has already transformed into MM.”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [10]

    The Introduction identifies SMM as an asymptomatic precursor of MM, and the Results section on timing reports a pre-existing clone in one SMM case. Neither passage addresses whether a significant fraction of SMM has already transformed into MM. Searches for progressive SMM, transformation, and a fraction of SMM found no supporting passage in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 28

  1. [1]Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol 2017; 14(2): 100– 13 doi 10.1038/nrclinonc.2016.122. 27531699 · DOI
  2. [2]Maura F, Bolli N, Rustad EH, Hultcrantz M, Munshi N, Landgren O. Moving From Cancer Burden to Cancer Genomics for Smoldering Myeloma: A Review. JAMA Oncol 2019 doi 10.1001/jamaoncol.2019.4659. PMC7430066 31830214 · DOI
  3. [3]Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Tian Ng AW, Wu Y, The repertoire of mutational signatures in human cancer. Nature 2020; 578(7793): 94– 101 doi 10.1038/s41586-020-1943-3. 32025018 PMC7054213 · DOI · Paper page
  4. [4]Bolli N, Maura F, Minvielle S, Gloznik D, Szalat R, Fullam A, Genomic patterns of progression in smoldering multiple myeloma. Nat Commun 2018; 9(1): 3363 doi 10.1038/s41467-018-05058-y. 30135448 PMC6105687 · DOI · Paper page
  5. [5]Maura F, Degasperi A, Nadeu F, Leongamornlert D, Davies H, Moore L, A practical guide for mutational signature analysis in hematological malignancies. Nat Commun 2019; 10(1): 2969 doi 10.1038/s41467-019-11037-8. 31278357 PMC6611883 · DOI · Paper page
  6. [6]Maura F, Rustad EH, Yellapantula V, Luksza M, Hoyos D, Maclachlan KH, Role of AID in the temporal pattern of acquisition of driver mutations in multiple myeloma. Leukemia 2019 doi 10.1038/s41375-019-0689-0. 31836853 · DOI · Paper page
  7. [7]Rustad EH, Yellapantula V, Leongamornlert D, Bolli N, Ledergor G, Nadeu F, Timing the initiation of multiple myeloma. Nat Commun 2020; 11(1): 1917 doi 10.1038/s41467-020-15740-9. 32317634 PMC7174344 · DOI · Paper page
  8. [9]Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood 2015; 125(20): 3069– 75 doi 10.1182/blood-2014-09-568899. 25838344 PMC4432003 · DOI
  9. [11]Landrigan PJ, Lioy PJ, Thurston G, Berkowitz G, Chen LC, Chillrud SN, Health and environmental consequences of the world trade center disaster. Environ Health Perspect 2004; 112(6): 731– 9 doi 10.1289/ehp.6702. 15121517 PMC1241968 · DOI
  10. [12]Kucab JE, Zou X, Morganella S, Joel M, Nanda AS, Nagy E, A Compendium of Mutational Signatures of Environmental Agents. Cell 2019; 177(4): 821– 36 e16 doi 10.1016/j.cell.2019.03.001. 30982602 PMC6506336 · DOI · Paper page
  11. [13]Li J, Brackbill RM, Liao TS, Qiao B, Cone JE, Farfel MR, Ten-year cancer incidence in rescue/recovery workers and civilians exposed to the September 11, 2001 terrorist attacks on the World Trade Center. Am J Ind Med 2016; 59(9): 709– 21 doi 10.1002/ajim.22638. 27582473 · DOI
  12. [14]Solan S, Wallenstein S, Shapiro M, Teitelbaum SL, Stevenson L, Kochman A, Cancer incidence in world trade center rescue and recovery workers, 2001–2008. Environ Health Perspect 2013; 121(6): 699– 704 doi 10.1289/ehp.1205894. 23613120 PMC3672914 · DOI
  13. [15]Zeig-Owens R, Webber MP, Hall CB, Schwartz T, Jaber N, Weakley J, Early assessment of cancer outcomes in New York City firefighters after the 9/11 attacks: an observational cohort study. Lancet 2011; 378(9794): 898– 905 doi 10.1016/S0140-6736(11)60989-6. 21890054 PMC5525140 · DOI
  14. [16]Landgren O, Zeig-Owens R, Giricz O, Goldfarb D, Murata K, Thoren K, Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster. JAMA Oncol 2018; 4(6): 821– 7 doi 10.1001/jamaoncol.2018.0509. 29710195 PMC6145680 · DOI · Paper page
  15. [17]Bolli F, Maura M, Minvielle M, Gloznik D, Szalat R, Fullam A, Genomic patterns of progression in smoldering multiple myeloma. Nat Commun 2018; 9 (1)(3363) doi 10.1038/s41467-018-05058-y. PMC6105687 30135448 · DOI · Paper page
  16. [18]Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, 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 PMC4241387 · DOI · Paper page
  17. [19]Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies FE, Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood 2018; 132(6): 587– 97 doi 10.1182/blood-2018-03-840132. 29884741 PMC6097138 · DOI · Paper page
  18. [20]Maura F, Bolli N, Angelopoulos N, Dawson KJ, Leongamornlert D, Martincorena I, Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun 2019; 10(1): 3835 doi 10.1038/s41467-019-11680-1. 31444325 PMC6707220 · DOI · Paper page
  19. [21]Rustad E, Yellapantula V, Glodzik D, Maclachlan K, Diamond B, Boyle E, Revealing the impact of recurrent and rare structural variants in multiple myeloma. Blood Cancer Discovery 2020; 1(3) 258– 273 doi 10.1158/2643-3230.BCD-20-0132. 33392515 PMC7774871 · DOI
  20. [22]Landau H, Yellapantula V, Diamond B, Rustad E, Maclachlan K, Gundem G, Accelerated single cell seeding in relapsed multiple myeloma. Nat Commun 2020; 11: 3617 doi 10.1038/s41467-020-17459-z 32680998 PMC7368016 · DOI
  21. [23]Jones D, Raine KM, Davies H, Tarpey PS, Butler AP, Teague JW, cgpCaVEManWrapper: Simple Execution of CaVEMan in Order to Detect Somatic Single Nucleotide Variants in NGS Data. Curr Protoc Bioinformatics 2016; 56: 15 0 1– 0 8 doi 10.1002/cpbi.20. PMC6097605 27930805 · DOI
  22. [24]Wala JA, Bandopadhayay P, Greenwald NF, O’Rourke R, Sharpe T, Stewart C, SvABA: genome-wide detection of structural variants and indels by local assembly. Genome Res 2018; 28(4): 581– 91 doi 10.1101/gr.221028.117. 29535149 PMC5880247 · DOI
  23. [25]Maura F, Rustad EH, Boyle EM, Morgan GJ. Reconstructing the evolutionary history of multiple myeloma. Best Pract Res Clin Haematol 2020; 33(1): 101145 doi 10.1016/j.beha.2020.101145. 32139011 PMC7389821 · DOI
  24. [26]Gerstung M, Jolly C, Leshchiner I, Dentro SC, Gonzalez S, Rosebrock D, The evolutionary history of 2,658 cancers. Nature 2020; 578(7793): 122– 8 doi 10.1038/s41586-019-1907-7. 32025013 PMC7054212 · DOI · Paper page
  25. [27]Maura F, Petljak M, Lionetti M, Cifola I, Liang W, Pinatel E, Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines. Leukemia 2017 doi 10.1038/leu.2017.345. PMC5886048 29209044 · DOI
  26. [28]Mitchell TJ, Turajlic S, Rowan A, Nicol D, Farmery JHR, O’Brien T, Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal. Cell 2018; 173(3): 611– 23 e17 doi 10.1016/j.cell.2018.02.020. 29656891 PMC5927631 · DOI
  27. [29]Alexandrov LB, Jones PH, Wedge DC, Sale JE, Campbell PJ, Nik-Zainal S, Clock-like mutational processes in human somatic cells. Nat Genet 2015; 47(12): 1402– 7 doi 10.1038/ng.3441. 26551669 PMC4783858 · DOI
  28. [31]Degasperi A, Amarante TD, Czarnecki J, Shooter S, Zou X, Glodzik D, A practical framework and online tool for mutational signature analyses show inter-tissue variation and driver dependencies. Nat Cancer 2020; 1(2): 249– 63 doi 10.1038/s43018-020-0027-5. 32118208 PMC7048622 · DOI · Paper page

Cited by

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Authors
Maura, F., Diamond, B., Maclachlan, K. H., Derkach, A., Yellapantula, V. D., Rustad, E. H., Hultcrantz, M., Shah, U. A., Hong, J., Landau, H. J., Iacobuzio-Donahue, C. A., Papaemmanuil, E., Irby, S., Crowley, L., Crane, M., Webber, M. P., Goldfarb, D. G., Zeig-Owens, R., Giricz, O., Verma, A., Prezant, D. J., Dogan, A., Shah, S. P., Zhang, Y., & Landgren, O.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • 6Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Icahn School of Medicine at Mount Sinai (US)
  • Albert Einstein College of Medicine (US)
  • New York City Fire Department (US)
  • 8Department of Medicine, Montefiore Medical Center, Bronx, New York.
  • 13Hematopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Corresponding author
  • Maura, Francesco
  • Landgren, Ola
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2021-01-27
Volume
27
Issue
7
Pages
2111-2118
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-20-2245
PMC
PMC8026670
OpenAlex
W3125655436
Cited by
10
References
3
Citations by year
2025: 5 · 2022: 1 · 2021: 4
FWCI
0.81
Type
journal article
Language
en
Open access
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Sylvester Comprehensive Cancer Center (P30 CA 240139)
  • Memorial Sloan Kettering Cancer Center (P30 CA 008748)
  • American Society of Hematology, the International Myeloma Foundation
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords
plasma cell neoplasms, multiple myeloma, World Trade Center disaster, September 11, 2001, first responders, environmental carcinogen exposure, mutational signatures, chromosomal gains
MeSH terms
Whole Genome Sequencing, Aged, Carcinogens, Environmental, Environmental Exposure, Humans, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide, September 11 Terrorist Attacks, Neoplasms, Plasma Cell, Emergency Responders

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