@article{208c8aafc37841fdaffc22088dd80900,
title = "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",
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 theWTCexposure that may have initiated or contributed to progression of malignancy.",
author = "Francesco Maura and Benjamin Diamond and Maclachlan, {Kylee H.} and Andriy Derkach and Yellapantula, {Venkata D.} and Rustad, {Even H.} and Malin Hultcrantz and Shah, {Urvi A.} and Jessica Hong and Landau, {Heather J.} and Iacobuzio-Donahue, {Christine A.} and Elli Papaemmanuil and Shani Irby and Laura Crowley and Michael Crane and Webber, {Mayris P.} and Goldfarb, {David G.} and Rachel Zeig-Owens and Orsi Giricz and Amit Verma and Prezant, {David J.} and Ahmet Dogan and Shah, {Sohrab P.} and Yanming Zhang and Ola Landgren",
note = "Funding Information: M. Hultcrantz reports grants from Memorial Sloan Kettering and the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748) during the conduct of the study. M. Hultcrantz also reports grants from Swedish Blood Cancer Funding Information: Foundation and Karolinska Institute Foundations, and personal fees from Curio Science and Intellisphere, LLC, outside the submitted work. U.A. Shah reports grants from Parker Institute for Cancer Immunotherapy, Celgene/BMS, and Janssen, and personal fees from Physicians Education Resources outside the submitted work. H.J. Landau reports grants from Genzyme Corporation, Amgen, Takeda Pharmaceuticals, Janssen Scientific Affairs LLC, HCA Healthcare, Spectrum Pharmaceuticals, Inc, Caelum Biosciences, Inc, Celgene, Clinical Care Options, and Karyopharm outside the submitted work. C.A. Iacobuzio-Donahue reports grants from Bristol Myers Squibb outside the submitted work. E. Papaemmanuil reports a patent for algorithm for WGS analytics pending to Isabl and equity holder of Isabl, a WGS analytics company that licenses the technology used at least, in part, to generate the data used in this study. L. Crowley reports other from World Trade Center Health Program during the conduct of the study and outside the submitted work. D.J. Prezant reports grants from National Institute of Occupation Safety & Health and CDC during the conduct of the study. A. Dogan reports grants from Roche, grants and personal fees from Takeda, nonfinancial support from AbbVie, and personal fees from Seattle Genetics, PER, EUSA Pharma, and PeerView outside the submitted work. S.P. Shah reports personal fees from Canexia Health Inc outside the submitted work. O. Landgren reports grants from Memorial Sloan Kettering and the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748) during the conduct of the study. O. Landgren also reports grants from Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm, FDA, Multiple Myeloma Research Foundation, International Myeloma Foundation, Leukemia and Lymphoma Society, Perelman Family Foundation, and Rising Tide Foundation; personal fees from Adaptive Biotech, Amgen, Binding Site, Bristol Myers Squibb, Celgene, Cellectis, Glenmark, Janssen, Juno, and Pfizer; and other from Takeda, Merck, Janssen, and Theradex outside the submitted work. No disclosures were reported by the other authors. Funding Information: This work was supported by the Society of Memorial Sloan Kettering, the Sylvester Comprehensive Cancer Center NCI Core Grant (P30 CA 240139), and the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748). F. Maura was supported by the American Society of Hematology, the International Myeloma Foundation, and The Society of Memorial Sloan Kettering Cancer Center. B. Diamond was supported by Conquer Cancer and the ASCO Foundation. K.H. Maclachlan was supported by the Haematology Society of Australia, New Zealand New Investigator Scholarship, the Royal College of Pathologists of Australasia Mike, and Carole Ralston Travelling Fellowship Award. We thank Integrated Genomics Operation for the sequencing support. Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",
year = "2021",
month = apr,
doi = "10.1158/1078-0432.CCR-20-2245",
language = "English",
volume = "27",
pages = "2111--2118",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "7",
}