Thread by @FrancescoMaura4

Check out our new study: 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 clincancerres.aacrjournals.org/content/early/… @DrOlaLandgren @sloan_kettering @SylvesterCancer #mmsm (1/10)

The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens.
In 2019 @DrOlaLandgren together with @FDNY showed a high incidence of MM and precursors among first responders to the WTC disaster (2/10)

Using whole genome sequencing (WGS) it is possible to define which are the main mutational processes (i.e., mutational signatures) active in each patient. We recently identified 7 main mutational signatures in newly diagnosed MM rdcu.be/cemZN (3/10)

Some of the WTC carcinogens (e.g., PAHs) have been reported to leave unique mutational signatures on the genome of human cells, allowing for quantification of the mutational burden for which they are responsible doi.org/10.1016/j.cell… @SerenaNikZainal (4/10)

Basing on this, we were motivated to identify distinct genomic signatures responsible for this increased risk and so we performed the first WGS characterization of plasma cell neoplasms in first responders and recovery workers exposed to the WTC attack (N=9) (5/10)

No significant differences were observed in comparing the post-WTC driver and mutational signatures landscape with 110 WGS from 56 patients with MM and the CoMMpass WGS (N=752) (6/10)

This suggests that the carcinogens present in the WTC debris may promote the development of myeloma through alternate evolutionary trajectories and a combination of drivers, without leaving direct mutagenic evidence (7/10)

Leveraging constant activity of the mutational signatures 1 and 5 overtime (clock-like), we estimated that tumor-initiating chromosomal gains were windowed to both pre-and post-WTC exposure (8/10)

This suggests that WTC exposure might, in some cases, have had a role in promoting a pre-existing clonal entity and, in others, it may have contributed to creating the conditions required for initiating the clonal entity (9/10)

This study would have not been possible without the support of the @SocietyofMSKCC, @sloan_kettering, @SylvesterCancer, @FDNY, and our strong network of collaborators at NYC medical institutions (10/10)