Tumor analysis of MMR genes in Lynch-like syndrome

Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. M...

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Detalles Bibliográficos
Autores: Rofes, Paula|||0000-0001-6045-7879, Dueñas Cid, Nuria|||0000-0001-6624-3265, Del Valle, Jesús|||0000-0003-3607-7045, Navarro, Matilde, Balmaña Gelpí, Judith|||0000-0002-0762-6415, Ramon y Cajal, Teresa|||0000-0003-3490-3585, Tuset, Noemí, Castillo, Carmen, González, Sara, Brunet, Joan|||0000-0003-1945-3512, Capella, Gabriel|||0000-0002-4669-7320, Lázaro García, Conxi|||0000-0002-7198-5906, Pineda, Marta|||0000-0002-5403-5845
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:306324
Acceso en línea:https://ddd.uab.cat/record/306324
https://dx.doi.org/urn:doi:10.1002/cam4.7041
Access Level:acceso abierto
Palabra clave:Lynch syndrome
Lynch-like syndrome
Clinical management
Mismatch repair genes
Mismatch repair-deficiency
Tumor testing
Descripción
Sumario:Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. Methods: Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%). Results and Discussion: More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.

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