Evidence map›Paper›PMID 31208405›Full record

ArticleBMC medical genomics2019

Retrovirus insertion site analysis of LGL leukemia patient genomes.

Weiling Li, Lei Yang, Robert S Harris, Lin Lin, Thomas L Olson, Cait E Hamele, David J Feith, Thomas P Loughran, Mary Poss

Open access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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  5. Mosaicism in Human Health and Disease.Annual review of genetics · 2020
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Weiling LiThe School of Electrical Engineering and Computer Science, The Pennsylvania State University, University Park, PA, 16802, USA.
Lei YangDepartment of Biology, The Pennsylvania State University, University Park, PA, 16802, USA.
Robert S HarrisDepartment of Biology, The Pennsylvania State University, University Park, PA, 16802, USA.
Lin LinDepartment of Statistics, The Pennsylvania State University, University Park, PA, 16802, USA.
Thomas L OlsonUniversity of Virginia Cancer Center and Department of Medicine, Division of Hematology & Oncology, University of Virginia, Charlottesville, Virginia, 22908, USA.
Cait E HameleUniversity of Virginia Cancer Center and Department of Medicine, Division of Hematology & Oncology, University of Virginia, Charlottesville, Virginia, 22908, USA.
David J FeithUniversity of Virginia Cancer Center and Department of Medicine, Division of Hematology & Oncology, University of Virginia, Charlottesville, Virginia, 22908, USA.
Thomas P LoughranUniversity of Virginia Cancer Center and Department of Medicine, Division of Hematology & Oncology, University of Virginia, Charlottesville, Virginia, 22908, USA.
Mary PossDepartment of Biology, The Pennsylvania State University, University Park, PA, 16802, USA. maryposs@gmail.com.ORCID 0000-0003-4147-2410
Pennsylvania State University · USUniversity of Virginia Cancer Center

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
Genomic Architecture of LGL LeukemiaR01CA178393 · NCI · UNIVERSITY OF VIRGINIA · PI Thomas P. Loughran, Aakrosh Ratan · 2016 to 2026
$6.5M
Characterization of the LGL Leukemia Virus (PQ 12)R01CA170334 · NCI · UNIVERSITY OF VIRGINIA · PI LOUGHRAN, THOMAS P., POSS, MARY L. · 2012 to 2015
$1.6M
NCI NIH HHS P30 CA044579NCI NIH HHS R01 CA170334NCI NIH HHS R01 CA178393
6 · The paper itself

Abstract

backgroundLarge granular lymphocyte (LGL) leukemia is an uncommon cancer characterized by sustained clonal proliferation of LGL cells. Antibodies reactive to retroviruses have been documented in the serum of patients with LGL leukemia. Culture or molecular approaches have to date not been successful in identifying a retrovirus.

methodsBecause a retrovirus must integrate into the genome of an infected cell, we focused our efforts on detecting a novel retrovirus integration site in the clonally expanded LGL cells. We present a new computational tool that uses long-insert mate pair sequence data to search the genome of LGL leukemia cells for retrovirus integration sites. We also utilize recently published methods to interrogate the status of polymorphic human endogenous retrovirus type K (HERV-K) provirus in patient genomes.

resultsOur data show that there are no new retrovirus insertions in LGL genomes of LGL leukemia patients. However, our insertion call tool did detect four HERV-K provirus integration sites that are polymorphic in the human population but absent from the human reference genome, hg19. To determine if the prevalence of these or other polymorphic proviral HERV-Ks differed between LGL leukemia patients and the general population, we used a recently developed tool that reports sites in the human genome occupied by a known proviral HERV-K. We report that there are significant differences in the number of polymorphic HERV-Ks in the genomes of LGL leukemia patients of European origin compared to individuals with European ancestry in the 1000 genomes (KGP) data.

conclusionsOur study confirms that the clonal expansion of LGL cells in LGL leukemia is not driven by the integration of a new infectious or endogenous retrovirus, although we do not rule out that these cells are responding to retroviral antigens produced in other cell types. However, our computational analyses revealed that the genomes of LGL leukemia patients carry a higher burden of polymorphic HERV-K proviruses compare to individuals from KGP of European ancestry. Our research emphasizes the merits of comprehensive genomic assessment of HERV-K in cancer samples and suggests that further analyses to determine contributions of HERV-K to LGL leukemia are warranted.

Indexed as

Genome, HumanHumansLeukemia, Large Granular LymphocyticProvirusesRetroviridaeVirus IntegrationGenomic insertionHERV-KLarge granular lymphocyte leukemiaRetrovirusVisualization tool

Identifiers

PMID31208405
PMCPMC6580525
OpenAlexW2952219569

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.