Syndrome de LYNCH : identification et prise en charge

Coffin, Elise; Dhooge, Marion; Ali, Einas Abou; Dermine, Solène; Lavolé, Julie; Chaussade, Stanislas

doi:10.1016/j.lpm.2019.07.011

Cited by 6 publications

(2 citation statements)

References 25 publications

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“…Moreover, the heterozygous status of this variant has been confirmed since the variant was detected in a heterozygous status in his sister (ID: IV‐5). For variant carriers, clinical surveillance should be offered following recommendations including colonoscopy with indigo carmine staining every 2 years starting from the age of 25, gynecological examination with pelvic examination, pelvic ultrasound by external and trans‐vaginal and endometrial biopsies once a year from the age of 30 (Coffin et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene

Bouras,

Legrand,

Kourda

et al. 2023

Molec Gen & Gen Med

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BackgroundThe MLH1 gene is one of the DNA mismatch repair genes (MMR), implicated in Lynch syndrome (LS), an autosomal dominant hereditary tumor susceptibility disease. The advent of next‐generation sequencing (NGS) technologies has accelerated the diagnosis of inherited diseases and increased the percentage of diagnosis of inherited cancers. However, some complex genomic alterations require the combination of several analytical strategies to allow correct biological interpretations. Here, we describe a novel MLH1 deletion and its pathogenicity determination in a patient suspected of LS.MethodsThe index case was a French 73‐year‐old man diagnosed with colorectal cancer displaying microsatellite instability and the loss of MLH1 and PMS2 expression. NGS analysis was used as the primary method for MMR genes screening. Long‐range PCR and reverse transcriptase polymerase chain reaction (RT‐PCR) were used for breakpoints and pathogenicity determinations.ResultsA large genomic deletion was detected which removed the last six nucleotides of MLH1 exon 11 together with a large part of intron 11. It was initially considered as a variant of unknown significance (VUS). Genomic breakpoints were subsequently characterized defining the deletion as c.1033_1039‐248del. Further RNA analysis demonstrated that this variant activated a cryptic donor splice site at the 5′ of the breakpoint, leading to a premature truncated protein: p.Thr345Alafs*13.ConclusionOur finding suggested that although NGS technologies have increased variant detection yield, combined approaches were still needed for complex variant characterization and pathogenicity assessment.

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Section: Discussionmentioning

confidence: 99%

From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene

Bouras,

Legrand,

Kourda

et al. 2023

Molec Gen & Gen Med

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show abstract

“…In the context of tumor biology, MSI is a marker of Lynch syndrome and a prognostic marker for CRC and other cancers such as endometrial cancers. Today only two techniques are validated to determine microsatellite/MMR status: immunohistochemistry (IHC) to detect the loss of MMR protein expression and molecular testing to assess fragment size variation of microsatellite loci (4). These techniques have some limitations including the fact that such experiments require significant quantities of DNA, are time-consuming and present limited sensitivity especially in the case of low tumor cell content within the sample.…”

Section: Introductionmentioning

confidence: 99%

Detection of Microsatellite Instability in Colorectal Cancer Tissue and Plasma samples using a new Multiplex Droplet Digital PCR kit

Evrard,

Chaba,

Abdelli

et al. 2024

Preprint

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Management of colorectal cancer (CRC) patients relies on the accurate determination of microsatellite instability (MSI) status. MSI status can have an influence on therapy decisions centered on immune checkpoint inhibitors. In this study a novel droplet digital PCR (ddPCR) kit for MSI status determination was validated across 2 separate CRC patient cohorts: 102 tumor samples from the ALGECOLS cohort and 129 plasma samples from the RASANC cohort. Each cohort was assessed for MSI status using the novel ddPCR kit and compared to historical and/or newly obtained results, (either immunohistochemistry analysis or PCR amplification). Concordance between ddPCR and conventional MSI determination methods for the analysis of tissue samples was 97.1% for ALGECOLS. When looking at positive ctDNA samples, a strong concordance was observed for the RASANC cohort. This study illustrates that ddPCR MSI testing represents a rapid, sensitive and accurate method with a strong correlation to established methods. Moreover, the ability of the described approach to monitor MSI status in both tumor and plasma enhances the potential for the use of MSI status in longitudinal monitoring of CRC patients.

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A PMS2 non-canonical splicing site variant leads to aberrant splicing in a patient suspected for lynch syndrome

et al. 2022

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Syndrome de LYNCH : identification et prise en charge

Cited by 6 publications

References 25 publications

From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene

From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene

Detection of Microsatellite Instability in Colorectal Cancer Tissue and Plasma samples using a new Multiplex Droplet Digital PCR kit

A PMS2 non-canonical splicing site variant leads to aberrant splicing in a patient suspected for lynch syndrome

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