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Jason Sheltzer: Tumors from Black cancer patients exhibit an increased frequency of whole-genome duplication events
Nov 14, 2023, 18:44

Jason Sheltzer: Tumors from Black cancer patients exhibit an increased frequency of whole-genome duplication events

Jason Sheltzer, Assistant professor at Yale School of Medicine, shared a post by medRxiv on Twitter, adding:

“New from my lab: we discovered that tumors from Black cancer patients exhibit an increased frequency of whole-genome duplication events, and we found that these alterations may contribute to racial differences in patient outcome.

To back up, Black patients have higher rates of cancer mortality than any other major racial or ethnic group in the US. These disparities may be caused by a combination of social, environmental, and genetic factors that influence cancer development and treatment.
For instance, Black patients tend to get worse treatment – they’re less likely to be seen by the best surgeons and they have to wait longer to start chemotherapy compared to white patients. This undoubtedly contributes to the outcome disparities.
From a genetic perspective, many groups have looked for differences in the frequency of point mutations between patient populations (see the recent paper below). But almost nothing is known about differences in aneuploidy – my lab’s focus.
We assembled a large dataset of tumors from Black and white patients, and we looked for differences in chromosome copy number. We discovered that across several independent cohorts, Black cancer patients were more likely to exhibit whole-genome duplications:
Whole-genome duplications (WGDs) are a genomic event in which a cell’s chromosome complement doubles – they go from ~2N to ~4N. These events are associated with increased genetic heterogeneity and aggressive disease.

We did some additional sub-analyses, and we couldn’t find any genetic explanation for the increase in WGD events in Black patients. We think that it may be caused by carcinogen exposure that is concentrated in minority communities – more on this later.

Next, we looked at the clinical correlates of WGDs. Black patients had worse outcomes than white patients, and WGD status was also associated with shorter survival. However, among the subset of patients with WGD-positive disease, there was no significant difference in survival.

We saw some additional interesting clinical correlations – for instance, both race and WGD status are associated with a lower incidence of MSI-high disease, and MSI-high status is an established biomarker for favorable outcomes.

In total, these results identify a factor that may be contributing to cancer disparities in the US, and they also underscore the importance of analyzing more than just point mutations in cancer sequencing projects.
Quoting medRxiv‘s post:
“An elevated rate of whole-genome duplication events in cancers from Black patients”

For details click here.
Source: Jason Sheltzer/Twitter