MSH3 : a confirmed predisposing gene for adenomatous polyposis.

Autor:	Villy MC; Department of Genetics, Université Paris Cité, Institut Curie, Paris, France marie-charlotte.villy@curie.fr., Masliah-Planchon J; Department of Genetics, PSL University, Institut Curie, Paris, France., Schnitzler A; Department of Genetics, PSL University, Institut Curie, Paris, France., Delhomelle H; Department of Genetics, PSL University, Institut Curie, Paris, France., Buecher B; Department of Genetics, PSL University, Institut Curie, Paris, France., Filser M; Department of Genetics, PSL University, Institut Curie, Paris, France., Merchadou K; Clinical Bioinformatics Unit, Institut Curie, Paris, France., Golmard L; Department of Genetics, PSL University, Institut Curie, Paris, France., Melaabi S; Department of Genetics, PSL University, Institut Curie, Paris, France., Vacher S; Department of Genetics, PSL University, Institut Curie, Paris, France., Blanluet M; Department of Genetics, PSL University, Institut Curie, Paris, France., Suybeng V; Department of Genetics, PSL University, Institut Curie, Paris, France., Corsini C; Medical Genetics Department, Centre Hospitalier Regional Universitaire de Montpellier, Montpellier, France., Dhooge M; Oncogenetic Unit, Department of Gastroenterology, AP-HP Centre-Université de Paris, Hopital Cochin, Paris, France., Hamzaoui N; Department of Genetics, AP-HP Centre-Université de Paris, Hospital Cochin, Paris, France., Farelly S; Oncogenetic Unit, Department of Gastroenterology, AP-HP Centre-Université de Paris, Hopital Cochin, Paris, France., Ait Omar A; Department of Gastroenterology, Hôpital Avicenne, Bobigny, France., Benamouzig R; Department of Gastroenterology, Hôpital Avicenne, Bobigny, France., Caumette V; Department of Genetics, Hôpitaux Universitaires Henri Mondor, Creteil, France., Bahuau M; Department of Genetics, Hôpitaux Universitaires Henri Mondor, Creteil, France., Cucherousset J; Department of Pathology, GHI Le Raincy-Montfermeil, Montfermeil, France., Allory Y; Department of Pathology, Université Paris-Saclay, Institut Curie, Paris, France., Stoppa-Lyonnet D; Department of Genetics, Université Paris Cité, Institut Curie, Paris, France., Bieche I; Department of Genetics, Université Paris Cité, Institut Curie, Paris, France., Colas C; Department of Genetics, PSL University, Institut Curie, Paris, France.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2023 Nov 27; Vol. 60 (12), pp. 1198-1205. Date of Electronic Publication: 2023 Nov 27.
DOI:	10.1136/jmg-2023-109341
Abstrakt:	Background: The MSH3 gene is part of the DNA mismatch repair system, but has never been shown to be involved in Lynch syndrome. A first report of four patients from two families, bearing biallelic MSH3 germline variants, with a phenotype of attenuated colorectal adenomatous polyposis raised the question of its involvement in hereditary cancer predisposition. The patients' tumours exhibited elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), a hallmark of MSH3 deficiency. Methods: We report five new unrelated patients with MSH3 -associated polyposis. We describe their personal and familial history and study the EMAST phenotype in various normal and tumour samples, which are relevant findings based on the rarity of this polyposis subtype so far. Results: All patients had attenuated colorectal adenomatous polyposis, with duodenal polyposis in two cases. Both women had breast carcinomas. EMAST phenotype was present at various levels in different samples of the five patients, confirming the MSH3 deficiency, with a gradient of instability in polyps depending on their degree of dysplasia. The negative EMAST phenotype ruled out the diagnosis of germline MSH3 deficiency for two patients: one homozygous for a benign variant and one with a monoallelic large deletion. Conclusion: This report lends further credence to biallelic MSH3 germline pathogenic variants being involved in colorectal and duodenal adenomatous polyposis. Large-scale studies may help clarify the tumour spectrum and associated risks. Ascertainment of EMAST may help with the interpretation of variants of unknown significance. We recommend adding MSH3 to dedicated diagnostic gene panels. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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