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SETD2 Haploinsufficiency Enhances Germinal Center–Associated AICDA Somatic Hypermutation to Drive B-cell Lymphomagenesis

Overview of attention for article published in Cancer Discovery, April 2022
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

Mentioned by

news
12 news outlets
blogs
1 blog
twitter
30 tweeters

Citations

dimensions_citation
1 Dimensions

Readers on

mendeley
9 Mendeley
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Title
SETD2 Haploinsufficiency Enhances Germinal Center–Associated AICDA Somatic Hypermutation to Drive B-cell Lymphomagenesis
Published in
Cancer Discovery, April 2022
DOI 10.1158/2159-8290.cd-21-1514
Pubmed ID
Authors

Wilfred Leung, Matt Teater, Ceyda Durmaz, Cem Meydan, Alexandra G. Chivu, Amy Chadburn, Edward J. Rice, Ashlesha Muley, Jeannie M. Camarillo, Jaison Arivalagan, Ziyi Li, Christopher R. Flowers, Neil L. Kelleher, Charles G. Danko, Marcin Imielinski, Sandeep S. Dave, Scott A. Armstrong, Christopher E. Mason, Ari M. Melnick

Abstract

SETD2 is the sole histone methyltransferase responsible for H3K36me3, with roles in splicing, transcription initiation and DNA damage response. Homozygous disruption of SETD2 yields a tumor suppressor effect in various cancers. However, SETD2 mutation is typically heterozygous in DLBCL. Here we show that heterozygous SETD2 deficiency results in GC hyperplasia, increased competitive fitness, with reduced DNA damage checkpoint activity and apoptosis, resulting in accelerated lymphomagenesis. Impaired DNA damage sensing in Setd2 haploinsufficient GCB and lymphoma cells associated with increased AICDA induced somatic hypermutation, complex structural variants, and increased translocations including those activating MYC. DNA damage was selectively increased on the non-template strand and H3K36me3 loss was associated with greater RNAPII processivity and mutational burden, suggesting that SETD2 mediated H3K36me3 is required for proper sensing of cytosine deamination. Hence, Setd2 haploinsufficiency delineates a novel GCB context specific oncogenic pathway involving defective epigenetic surveillance of AICDA mediated effects on transcribed genes.

Twitter Demographics

The data shown below were collected from the profiles of 30 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 9 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 33%
Professor 1 11%
Student > Doctoral Student 1 11%
Student > Postgraduate 1 11%
Student > Master 1 11%
Other 0 0%
Unknown 2 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 44%
Medicine and Dentistry 2 22%
Neuroscience 1 11%
Agricultural and Biological Sciences 1 11%
Unknown 1 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 108. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 August 2022.
All research outputs
#301,670
of 21,751,441 outputs
Outputs from Cancer Discovery
#132
of 3,485 outputs
Outputs of similar age
#7,842
of 341,354 outputs
Outputs of similar age from Cancer Discovery
#11
of 126 outputs
Altmetric has tracked 21,751,441 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,485 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.6. This one has done particularly well, scoring higher than 96% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,354 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 126 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.