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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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
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spelling Tumor analysis of MMR genes in Lynch-like syndromeChallenges associated with results interpretationRofes, Paula|||0000-0001-6045-7879Dueñas Cid, Nuria|||0000-0001-6624-3265Del Valle, Jesús|||0000-0003-3607-7045Navarro, MatildeBalmaña Gelpí, Judith|||0000-0002-0762-6415Ramon y Cajal, Teresa|||0000-0003-3490-3585Tuset, NoemíCastillo, CarmenGonzález, SaraBrunet, Joan|||0000-0003-1945-3512Capella, Gabriel|||0000-0002-4669-7320Lázaro García, Conxi|||0000-0002-7198-5906Pineda, Marta|||0000-0002-5403-5845Lynch syndromeLynch-like syndromeClinical managementMismatch repair genesMismatch repair-deficiencyTumor testingUp 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.Universitat Autònoma de Barcelona 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/306324https://dx.doi.org/urn:doi:10.1002/cam4.7041reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00553Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-111254RB-I00Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/12/00234open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3063242026-06-06T12:50:31Z
dc.title.none.fl_str_mv Tumor analysis of MMR genes in Lynch-like syndrome
Challenges associated with results interpretation
title Tumor analysis of MMR genes in Lynch-like syndrome
spellingShingle Tumor analysis of MMR genes in Lynch-like syndrome
Rofes, Paula|||0000-0001-6045-7879
Lynch syndrome
Lynch-like syndrome
Clinical management
Mismatch repair genes
Mismatch repair-deficiency
Tumor testing
title_short Tumor analysis of MMR genes in Lynch-like syndrome
title_full Tumor analysis of MMR genes in Lynch-like syndrome
title_fullStr Tumor analysis of MMR genes in Lynch-like syndrome
title_full_unstemmed Tumor analysis of MMR genes in Lynch-like syndrome
title_sort Tumor analysis of MMR genes in Lynch-like syndrome
dc.creator.none.fl_str_mv 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
author Rofes, Paula|||0000-0001-6045-7879
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Lynch syndrome
Lynch-like syndrome
Clinical management
Mismatch repair genes
Mismatch repair-deficiency
Tumor testing
topic Lynch syndrome
Lynch-like syndrome
Clinical management
Mismatch repair genes
Mismatch repair-deficiency
Tumor testing
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/306324
https://dx.doi.org/urn:doi:10.1002/cam4.7041
url https://ddd.uab.cat/record/306324
https://dx.doi.org/urn:doi:10.1002/cam4.7041
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00553
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-111254RB-I00
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/12/00234
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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