Evidence map›Paper›PMID 37318702›Full record

ArticleFamilial cancer2023

A mosaic pathogenic variant in MSH6 causes MSH6-deficient colorectal and endometrial cancer in a patient classified as suspected Lynch syndrome: a case report.

Romy Walker, Mark Clendenning, Jihoon E Joo, Jessie Xue, Khalid Mahmood, Peter Georgeson, Julia Como, Sharelle Joseland, Susan G Preston, James M Chan and 7 more

Open access · hybridAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Familial cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

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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

17 authors at 4 institutions in 1 country.

Romy WalkerColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia. romy.walker@unimelb.edu.au.
Mark ClendenningColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Jihoon E JooColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Jessie XueColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Khalid MahmoodColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Peter GeorgesonColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Julia ComoColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Sharelle JoselandColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Susan G PrestonColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
James M ChanColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Mark A JenkinsUniversity of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Christophe RostyColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Finlay A MacraeGenomic Medicine and Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, VIC, 3000, Australia.
Stephanie Di PalmaClinical Genetics Unit, Austin Health, Melbourne, VIC, 3084, Australia.
Ainsley CampbellClinical Genetics Unit, Austin Health, Melbourne, VIC, 3084, Australia.
Ingrid M WinshipGenomic Medicine and Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, VIC, 3000, Australia.
Daniel D BuchananColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, 305 Grattan Street, Parkville, VIC, 3010, Australia.
Victorian Comprehensive Cancer Centre · AUUniversity of Melbourne · AUAustin Health · AUMelbourne Bioinformatics · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. However, mosaic variants in the MMR genes have been rarely described. We identified a likely de novo mosaic MSH6:c.1135_1139del p.Arg379* pathogenic variant in a patient diagnosed with suspected Lynch syndrome/Lynch-like syndrome. The patient developed MSH6-deficient EC and CRC at 54 and 58 years of age, respectively, without a detectable germline MMR pathogenic variant. Multigene panel sequencing of tumor and blood-derived DNA identified an MSH6 somatic mutation (MSH6:c.1135_1139del p.Arg379*) common to both the EC and CRC, raising suspicion of mosaicism. A droplet digital polymerase chain reaction (ddPCR) assay detected the MSH6 variant at 5.34% frequency in normal colonic tissue, 3.49% in saliva and 1.64% in blood DNA, demonstrating the presence of the MSH6 variant in all three germ layers. This study highlights the utility of tumor sequencing to guide sensitive ddPCR testing to detect low-level mosaicism in the MMR genes. Further investigation of the prevalence of MMR mosaicism is needed to inform routine diagnostic approaches and genetic counselling.

Indexed as

Colorectal Neoplasms, Hereditary NonpolyposisEndometrial NeoplasmsDNADNA-Binding ProteinsDNA Mismatch RepairFemaleGerm-Line MutationHumansMicrosatellite InstabilityMutL Protein Homolog 1DNADNA-Binding ProteinsMutL Protein Homolog 1DNA mismatch repairDroplet digital PCRMosaicismMSH6Suspected Lynch syndromeTargeted tumor sequencing

Identifiers

PMID37318702
PMCPMC10541337
OpenAlexW4380730347

What OpenQuestion holds

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LicenceCC BY
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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.