Evidence map›Paper›PMID 38466935›Full record

ArticleJournal of the National Cancer Institute2024

Frameshift mutations in peripheral blood as a biomarker for surveillance of Lynch syndrome.

Yurong Song, Holli Loomans-Kropp, Ryan N Baugher, Brandon Somerville, Shaneen S Baxter, Travis D Kerr, Teri M Plona, Stephanie D Mellott, Todd B Young, Heidi E Lawhorn and 12 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Yurong SongVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID 0000-0001-7151-0575
Holli Loomans-KroppDivision of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
Ryan N BaugherMolecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Brandon SomervilleVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Shaneen S BaxterVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Travis D KerrVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Teri M PlonaMolecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Stephanie D MellottMolecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Todd B YoungMolecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Heidi E LawhornMolecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Lei WeiDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Qiang HuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Song LiuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Alan HutsonDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Ligia PintoVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
John D PotterPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID 0000-0001-5439-1500
Shizuko SeiDivision of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
Ozkan GelincikDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Steven M LipkinDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Johannes GebertDepartment of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Matthias KloorDepartment of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Robert H ShoemakerDivision of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.

Funding

Immuno-Oncology Translation Network: Data Management and Resource-Sharing Center at RPCIU24CA232979 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI HUTSON, ALAN DAVID, LIU, SONG · 2018 to 2024
$8.9M
YAP1 and RB1 cooperate to regulate lung cancer lineage plasticity and therapeutic resistanceU24CA274159 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI DAVID W. GOODRICH, Alan David Hutson · 2022 to 2026
$8.5M
The Computational Tumor Immunology Core (CTIC)U54CA272688 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Vivek Mittal · 2022 to 2026
$7.4M
IOTN Moonshot U24CA232979-01NCI ARTNet U24CA274159NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INCI NIH HHS HHSN261201500039CNCI NIH HHS U24 CA232979NCI NIH HHS U24 CA274159NCI NIH HHS U54 CA272688NCI PREVENT HHSN2612015000391
6 · The paper itself

Abstract

backgroundLynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome. Recurrent frameshift mutations in these regions are thought to play a central role in the increased risk of various cancers, but no biomarkers are currently available for the surveillance of high microsatellite instability-associated cancers.

methodsA frameshift mutation-based biomarker panel was developed and validated by targeted next-generation sequencing of supernatant DNA from cultured high microsatellite instability colorectal cancer cells. This panel supported selection of 122 frameshift mutation targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat samples (53 samples) and blood-derived cell-free DNA (cfDNA) (38 samples) obtained from 45 high microsatellite instability and mismatch repair-deficient patients. We also sequenced cfDNA from 84 healthy participants to assess background noise.

resultsRecurrent frameshift mutations at coding mononucleotide repeats were detectable not only in tumors but also in cfDNA from high microsatellite instability and mismatch repair-deficient patients, including a Lynch syndrome carrier, with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy participants. Receiver operating characteristic curve analysis showed high sensitivity and specificity (area under the curve = 0.94) of the investigated panel.

conclusionsWe demonstrated that frameshift mutations can be detected in cfDNA from high microsatellite instability and mismatch repair-deficient patients and asymptomatic carriers. The 122-target frameshift mutation panel described here has promise as a tool for improved surveillance of high microsatellite instability and mismatch repair-deficient patients, with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.

Indexed as

Biomarkers, TumorColorectal Neoplasms, Hereditary NonpolyposisFrameshift MutationMicrosatellite InstabilityAdultAgedCase-Control StudiesDNA Mismatch RepairFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedROC CurveSensitivity and SpecificityBiomarkers, Tumor

Identifiers

PMID38466935
PMCPMC11160491

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.