Evidence map›Paper›PMID 37267683›Full record

ArticleCancer genetics2023

Distinct mechanisms of PTEN inactivation in dogs and humans highlight convergent molecular events that drive cell division in the pathogenesis of osteosarcoma.

Aaron L Sarver, Lauren J Mills, Kelly M Makielski, Nuri A Temiz, Jinhua Wang, Logan G Spector, Subbaya Subramanian, Jaime F Modiano

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer genetics, 2023. 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
3.1field-weighted citation impact, top 9% 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, 12 citations in OpenAlex.

  1. Integrated Multiomic Profiling Enhances Risk Stratification and Prognostication in Canine Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  2. The oncogenome of the domestic cat.Science (New York, N.Y.) · 2026
    Article
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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

8 authors at 2 institutions in 1 country.

Aaron L SarverMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA. Electronic address: sarver@umn.edu.
Lauren J MillsMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Kelly M MakielskiMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA; Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN 55108, USA.
Nuri A TemizMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA.
Jinhua WangMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA.
Logan G SpectorMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA.
Subbaya SubramanianMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA; Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Jaime F ModianoMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA; Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN 55108, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Center for Engineering and Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
University of Minnesota · USUniversity of Minnesota Medical Center · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
Bioinformatics approaches to solve the "Missing Driver" problem in solid tumorsR50CA211249 · NCI · UNIVERSITY OF MINNESOTA · PI SARVER, AARON L · 2016 to 2020
$565k
(PQ3) Modulation of Osteosarcoma Biology by Inflammation and Immunity Defined through a ComparativeApproachR21CA208529 · NCI · UNIVERSITY OF MINNESOTA · PI MODIANO, JAIME F. · 2016 to 2017
$365k
NCI NIH HHS P30 CA077598NCI NIH HHS R21 CA208529NCI NIH HHS R50 CA211249NCI NIH HHS T32 CA009138
6 · The paper itself

Abstract

A hallmark of osteosarcoma in both human and canine tumors is somatic fragmentation and rearrangement of chromosome structure which leads to recurrent increases and decreases in DNA copy number. The PTEN gene has been implicated as an important tumor suppressor in osteosarcoma via forward genetic screens. Here, we analyzed copy number changes, promoter methylation and transcriptomes to better understand the role of PTEN in canine and human osteosarcoma. Reduction in PTEN copy number was observed in 23 of 95 (25%) of the canine tumors examined leading to corresponding decreases in PTEN transcript levels from RNA-Seq samples. Unexpectedly, canine tumors with an intact PTEN locus had higher levels of PTEN transcripts than human tumors. This variation in transcript abundance was used to evaluate the role of PTEN in osteosarcoma biology. Decreased PTEN copy number and transcript level was observed in - and likely an important driver of - increases in cell cycle transcripts in four independent canine transcriptional datasets. In human osteosarcoma, homozygous copy number loss was not observed, instead increased methylation of the PTEN promoter was associated with increased cell cycle transcripts. Somatic modification of PTEN, either by homozygous deletion in dogs or by promoter methylation in humans, is clinically relevant to osteosarcoma, because the cell cycle related transcripts are associated with patient outcomes. The PTEN gene is part of a syntenic rearrangement unique to the canine genome, making it susceptible to somatic loss of both copies of distal chromosome 26 which also includes the FAS death receptor. SIGNIFICANCE STATEMENT: PTEN function is abrogated by different mechanisms in canine and human osteosarcoma tumors leading to uncontrolled cell cycling. Somatic loss of this canine specific syntenic region may help explain why the canine genome appears to be uniquely susceptible to osteosarcoma. Syntenic arrangement, in the context of copy number change, may lead to synergistic interactions that in turn modify species specific cancer risk. Comparative models of tumorigenesis may utilize different driver mechanisms.

Indexed as

Bone NeoplasmsOsteosarcomaAnimalsCell DivisionDogsHomozygoteHumansPTEN PhosphohydrolaseSequence DeletionPTEN PhosphohydrolasePTEN protein, humanBioinformaticsCancerComparative genomicsGenomicsOsteosarcoma

Identifiers

PMID37267683
PMCPMC11694714
OpenAlexW4377141746

What OpenQuestion holds

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Registered trials

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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.