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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

2021; American Association for Cancer Research; Volume: 27; Issue: 7 Linguagem: Inglês

10.1158/1078-0432.ccr-20-2245

1557-3265

Francesco Maura, Benjamin Diamond, Kylee Maclachlan, Andriy Derkach, Venkata Yellapantula, Even H. Rustad, Malin Hultcrantz, Urvi A. Shah, Jessica Hong, Heather Landau, Christine A. Iacobuzio‐Donahue, Elli Papaemmanuil, Shani Irby, Laura Crowley, Michael Crane, Mayris P. Webber, David G. Goldfarb, Rachel Zeig‐Owens, Orsi Giricz, Amit Verma, David J. Prezant, Ahmet Doğan, Sohrab P. Shah, Yanming Zhang, Ola Landgren,

Carcinogens and Genotoxicity Assessment

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.