Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Maura Francesco, Diamond Benjamin, Maclachlan Kylee H, Derkach Andriy, Yellapantula Venkata D, Rustad Even H, Hultcrantz Malin, Shah Urvi A, Hong Jessica, Landau Heather J, Iacobuzio-Donahue Christine A, Papaemmanuil Elli, Irby Shani, Crowley Laura, Crane Michael, Webber Mayris P, Goldfarb David G, Zeig-Owens Rachel, Giricz Orsi, Verma Amit, Prezant David J, Dogan Ahmet, Shah Sohrab P, Zhang Yanming, Landgren Ola
Аннотация
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.
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.