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Loss of the DNA Repair Gene RNase H2 Identifies a Unique Subset of DDR-Deficient Leiomyosarcomas.

Overview of attention for article published in Molecular Cancer Therapeutics, April 2024
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  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

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Title
Loss of the DNA Repair Gene RNase H2 Identifies a Unique Subset of DDR-Deficient Leiomyosarcomas.
Published in
Molecular Cancer Therapeutics, April 2024
DOI 10.1158/1535-7163.mct-23-0761
Pubmed ID
Authors

Michael S Nakazawa, Ian M Silverman, Victoria Rimkunas, Artur Veloso, Dominik Glodzik, Adrienne Johnson, Toshiro K Ohsumi, Shreyaskumar R Patel, Anthony P Conley, Christina L Roland, Pamela T Soliman, Hannah C Beird, Chia-Chin Wu, Davis R Ingram, Rossana Lazcano, Dawon Song, Khalida M Wani, Alexander J Lazar, Timothy A Yap, Wei-Lien Wang, J Andrew Livingston

Abstract

Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for DDR targeted treatments. Therefore, we designed a protein and genomic based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor tissue microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS) (30%, 39/102). In the TCGA database, RNASEH2B homozygous deletions (HomDels) were found in 6% (5/80) of LMS cases, with a higher proportion in U-LMS (15%; 4/27) compared to ST-LMS (2%; 1/53). Using the SNiPDx targeted-NGS sequencing assay to detect biallelic loss of function in select DDR related genes, we found RNASEH2B HomDels in 54% (19/35) of U-LMS cases with RNase H2 loss by IHC, and 7% (3/43) HomDels in RNase H2 intact cases. No RNASEH2B HomDels were detected in ST-LMS. In U-LMS patient cohort (n = 109), no significant overall survival difference was seen in patients with RNase H2 loss versus intact, or RNASEH2B HomDel (n=12) vs Non-HomDel (n=37). The overall diagnostic accuracy, sensitivity, and specificity of RNase H2 IHC for detecting RNASEH2B HomDels in U-LMS was 76%, 93% and 71% respectively, and it is being developed for future predictive biomarker driven clinical trials targeting DDR in U-LMS.

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Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 April 2024.
All research outputs
#14,761,257
of 25,628,260 outputs
Outputs from Molecular Cancer Therapeutics
#2,887
of 4,083 outputs
Outputs of similar age
#54,908
of 156,319 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#7
of 15 outputs
Altmetric has tracked 25,628,260 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 4,083 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.9. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
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 156,319 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.