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Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1+/−-driven murine colonic adenomas

Overview of attention for article published in BMC Cancer, February 2020
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Title
Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1+/−-driven murine colonic adenomas
Published in
BMC Cancer, February 2020
DOI 10.1186/s12885-020-6616-y
Pubmed ID
Authors

Jessica L. Preston, Nicholas Stiffler

Abstract

The loss of a single copy of adenomatous polyposis coli (Apc) in leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1)-expressing colonic progenitor cells induces rapid growth of adenomas in mice with high penetrance and multiplicity. The tumors lack functional APC, and a genetic loss of heterozygosity of Apc was previously observed. To identify genomic features of early tumorigenesis, and to profile intertumoral genetic heterogeneity, tumor exome DNA (n = 9 tumors) and mRNA (n = 5 tumors) sequences were compared with matched nontumoral colon tissue. Putative somatic mutations were called after stringent variant filtering. Somatic signatures of mutational processes were determined and splicing patterns were observed. The adenomas were found to be genetically heterogeneous and unexpectedly hypermutated, displaying a strong bias toward G:C > A:T mutations. A genetic loss of heterozygosity of Apc was not observed, however, an epigenetic loss of heterozygosity was apparent in the tumor transcriptomes. Complex splicing patterns characterized by a loss of intron retention were observed uniformly across tumors. This study demonstrates that early tumors originating from intestinal stem cells with reduced Lrig1 and Apc expression are highly mutated and genetically heterogeneous, with an inflammation-associated mutational signature and complex splicing patterns that are uniform across tumors.

Twitter Demographics

The data shown below were collected from the profiles of 4 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 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 3 60%
Student > Bachelor 2 40%
Readers by discipline Count As %
Medicine and Dentistry 3 60%
Biochemistry, Genetics and Molecular Biology 1 20%
Veterinary Science and Veterinary Medicine 1 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 27 October 2020.
All research outputs
#10,098,447
of 17,520,458 outputs
Outputs from BMC Cancer
#2,351
of 6,386 outputs
Outputs of similar age
#131,824
of 267,573 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 17,520,458 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,386 research outputs from this source. They receive a mean Attention Score of 4.1. This one has gotten more attention than average, scoring higher than 62% 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 267,573 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them