Evidence map›Paper›PMID 37957483›Full record

ArticleFamilial cancer2024

Functional and phenotypic consequences of an unusual inversion in MSH2.

Dylan Pelletier, Abhijit Rath, Nelly Sabbaghian, Manuela Pelmus, Catherine Hudon, Karine Jacob, Leora Witowski, Avi Saskin, Christopher D Heinen, William D Foulkes

Abstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Familial cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 64% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

10 authors at 3 institutions in 2 countries.

Dylan Pelletier *Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.
Abhijit Rath *Center for Molecular Oncology, UConn Health, Farmington, CT, USA.
Nelly SabbaghianDepartment of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.
Manuela PelmusDepartment of Pathology, Medicine, McGill University, Montreal, QC, Canada.
Catherine HudonDepartment of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.
Karine JacobService de Médecine Génique, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
Leora WitowskiDepartment of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.
Avi SaskinService de Médecine Génique, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
Christopher D HeinenCenter for Molecular Oncology, UConn Health, Farmington, CT, USA. cheinen@uchc.edu.
William D FoulkesDepartment of Human Genetics, Medicine, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca.
McGill University · CAMolecular Oncology (United States) · USUniversité de Montréal · CA

Funding

Hereditary Cancer Variants of Uncertain Significance in Stem CellsR01CA222477 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HEINEN, CHRISTOPHER D. · 2019 to 2024
$1.9M
CIHR FDN-148390NCI NIH HHS R01 CA222477NIH HHS CA222477
6 · The paper itself

Abstract

Lynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2, MSH6, MLH1, PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 of MSH2. We further show that this variant is almost completely absent at the protein level, and that the associated cancers have complete loss of MSH2 and MSH6 expression by immunohistochemistry. Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.

Indexed as

AdenocarcinomaColorectal Neoplasms, Hereditary NonpolyposisAdultDNA Mismatch RepairExonsGerm-Line MutationHumansMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinMismatch Repair Endonuclease PMS2MSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinCRISPR/Cas9Germline inversionLynch syndromeMedical geneticsMismatch repairMSH2

Identifiers

PMID37957483
PMCPMC13338880
OpenAlexW4388646039

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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.