No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study
- Autores
- Dominguez Valentin, Mev; Plazzer, John Paul; Sampson, Julian R.; Engel, Christoph; Aretz, Stefan; Jenkins, Mark A.; Sunde, Lone; Bernstein, Inge; Capella, Gabriel; Balaguer Prunés, Francesc; Macrae, Finlay; Winship, Ingrid M.; Thomas, Huw; Evans, Dafydd Gareth; Burn, John; Greenblatt, Marc; de Vos tot Nederveen Cappel, Wouter H.; Sijmons, Rolf H.; Nielsen, Maartje; Bertario, Lucio; Bonanni, Bernardo; Tibiletti, Maria Grazia; Cavestro, Giulia Martina; Lindblom, Annika; Della Valle, Adriana; Lopez Kostner, Francisco; Alvarez, Karin; Gluck, Nathan; Katz, Lior; Heinimann, Karl; Piñero, Tamara Alejandra; Pavicic, Walter Hernan
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
Fil: Dominguez Valentin, Mev. St Mark’s Hospital; Reino Unido. The Norwegian Radium Hospital; Noruega. European Hereditary Tumour Group; Reino Unido
Fil: Plazzer, John Paul. St Mark’s Hospital; Reino Unido. The Royal Melbourne Hospital; Australia
Fil: Sampson, Julian R.. European Hereditary Tumour Group; Reino Unido. Cardiff University; Reino Unido
Fil: Engel, Christoph. European Hereditary Tumour Group; Reino Unido. Universitat Leipzig; Alemania
Fil: Aretz, Stefan. Universitat Bonn; Alemania
Fil: Jenkins, Mark A.. University of Melbourne; Australia
Fil: Sunde, Lone. Aalborg University; Dinamarca
Fil: Bernstein, Inge. Aalborg University; Dinamarca
Fil: Capella, Gabriel. European Hereditary Tumour Group; Reino Unido. St Mark’s Hospital; Reino Unido. Institut Català d’Oncologia; España
Fil: Balaguer Prunés, Francesc. Universidad de Barcelona; España
Fil: Macrae, Finlay. European Hereditary Tumour Group; Reino Unido. The Royal Melbourne Hospital; Australia
Fil: Winship, Ingrid M.. University of Melbourne; Australia
Fil: Thomas, Huw. Imperial College London; Reino Unido
Fil: Evans, Dafydd Gareth. University of Manchester; Reino Unido
Fil: Burn, John. Universidad de Newcastle; Australia. The Royal Melbourne Hospital; Australia. St Mark’s Hospital; Reino Unido
Fil: Greenblatt, Marc. University of Vermont; Estados Unidos
Fil: de Vos tot Nederveen Cappel, Wouter H.. Isala Clinics; Países Bajos
Fil: Sijmons, Rolf H.. University of Groningen; Países Bajos. St Mark’s Hospital; Reino Unido. European Hereditary Tumour Group; Reino Unido
Fil: Nielsen, Maartje. Leids Universitair Medisch Centrum; Países Bajos
Fil: Bertario, Lucio. Fondazione IRCCS Istituto Nazionale dei Tumori; Italia
Fil: Bonanni, Bernardo. Fondazione IRCCS Istituto Nazionale dei Tumori; Italia
Fil: Tibiletti, Maria Grazia. Università dell’Insubria; Italia
Fil: Cavestro, Giulia Martina. Vita-Salute San Raffaele University; Italia
Fil: Lindblom, Annika. Karolinska Huddinge Hospital; Suecia
Fil: Della Valle, Adriana. Hospital Fuerzas Armadas; Uruguay
Fil: Lopez Kostner, Francisco. Clínica Universidad de los Andes; Chile
Fil: Alvarez, Karin. Clínica Universidad de los Andes; Chile
Fil: Gluck, Nathan. Universitat Tel Aviv; Israel
Fil: Katz, Lior. Sheba Medical Center; Israel
Fil: Heinimann, Karl. University Hospital Basel; Suiza
Fil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina
Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina - Materia
-
ABERRANT SPLICING
CANCER INCIDENCE
LYNCH SYNDROME
MISSENSE
MLH1
MSH2
PENETRANCE
TRUNCATING - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/211951
Ver los metadatos del registro completo
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No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database studyDominguez Valentin, MevPlazzer, John PaulSampson, Julian R.Engel, ChristophAretz, StefanJenkins, Mark A.Sunde, LoneBernstein, IngeCapella, GabrielBalaguer Prunés, FrancescMacrae, FinlayWinship, Ingrid M.Thomas, HuwEvans, Dafydd GarethBurn, JohnGreenblatt, Marcde Vos tot Nederveen Cappel, Wouter H.Sijmons, Rolf H.Nielsen, MaartjeBertario, LucioBonanni, BernardoTibiletti, Maria GraziaCavestro, Giulia MartinaLindblom, AnnikaDella Valle, AdrianaLopez Kostner, FranciscoAlvarez, KarinGluck, NathanKatz, LiorHeinimann, KarlPiñero, Tamara AlejandraPavicic, Walter HernanABERRANT SPLICINGCANCER INCIDENCELYNCH SYNDROMEMISSENSEMLH1MSH2PENETRANCETRUNCATINGhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.Fil: Dominguez Valentin, Mev. St Mark’s Hospital; Reino Unido. The Norwegian Radium Hospital; Noruega. European Hereditary Tumour Group; Reino UnidoFil: Plazzer, John Paul. St Mark’s Hospital; Reino Unido. The Royal Melbourne Hospital; AustraliaFil: Sampson, Julian R.. European Hereditary Tumour Group; Reino Unido. Cardiff University; Reino UnidoFil: Engel, Christoph. European Hereditary Tumour Group; Reino Unido. Universitat Leipzig; AlemaniaFil: Aretz, Stefan. Universitat Bonn; AlemaniaFil: Jenkins, Mark A.. University of Melbourne; AustraliaFil: Sunde, Lone. Aalborg University; DinamarcaFil: Bernstein, Inge. Aalborg University; DinamarcaFil: Capella, Gabriel. European Hereditary Tumour Group; Reino Unido. St Mark’s Hospital; Reino Unido. Institut Català d’Oncologia; EspañaFil: Balaguer Prunés, Francesc. Universidad de Barcelona; EspañaFil: Macrae, Finlay. European Hereditary Tumour Group; Reino Unido. The Royal Melbourne Hospital; AustraliaFil: Winship, Ingrid M.. University of Melbourne; AustraliaFil: Thomas, Huw. Imperial College London; Reino UnidoFil: Evans, Dafydd Gareth. University of Manchester; Reino UnidoFil: Burn, John. Universidad de Newcastle; Australia. The Royal Melbourne Hospital; Australia. St Mark’s Hospital; Reino UnidoFil: Greenblatt, Marc. University of Vermont; Estados UnidosFil: de Vos tot Nederveen Cappel, Wouter H.. Isala Clinics; Países BajosFil: Sijmons, Rolf H.. University of Groningen; Países Bajos. St Mark’s Hospital; Reino Unido. European Hereditary Tumour Group; Reino UnidoFil: Nielsen, Maartje. Leids Universitair Medisch Centrum; Países BajosFil: Bertario, Lucio. Fondazione IRCCS Istituto Nazionale dei Tumori; ItaliaFil: Bonanni, Bernardo. Fondazione IRCCS Istituto Nazionale dei Tumori; ItaliaFil: Tibiletti, Maria Grazia. Università dell’Insubria; ItaliaFil: Cavestro, Giulia Martina. Vita-Salute San Raffaele University; ItaliaFil: Lindblom, Annika. Karolinska Huddinge Hospital; SueciaFil: Della Valle, Adriana. Hospital Fuerzas Armadas; UruguayFil: Lopez Kostner, Francisco. Clínica Universidad de los Andes; ChileFil: Alvarez, Karin. Clínica Universidad de los Andes; ChileFil: Gluck, Nathan. Universitat Tel Aviv; IsraelFil: Katz, Lior. Sheba Medical Center; IsraelFil: Heinimann, Karl. University Hospital Basel; SuizaFil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaMultidisciplinary Digital Publishing Institute2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211951Dominguez Valentin, Mev; Plazzer, John Paul; Sampson, Julian R.; Engel, Christoph; Aretz, Stefan; et al.; No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study; Multidisciplinary Digital Publishing Institute; Journal of Clinical Medicine; 10; 13; 6-2021; 1-122077-0383CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2077-0383/10/13/2856info:eu-repo/semantics/altIdentifier/doi/10.3390/jcm10132856info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:37:16Zoai:ri.conicet.gov.ar:11336/211951instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:37:16.449CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| title |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| spellingShingle |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study Dominguez Valentin, Mev ABERRANT SPLICING CANCER INCIDENCE LYNCH SYNDROME MISSENSE MLH1 MSH2 PENETRANCE TRUNCATING |
| title_short |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| title_full |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| title_fullStr |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| title_full_unstemmed |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| title_sort |
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study |
| dc.creator.none.fl_str_mv |
Dominguez Valentin, Mev Plazzer, John Paul Sampson, Julian R. Engel, Christoph Aretz, Stefan Jenkins, Mark A. Sunde, Lone Bernstein, Inge Capella, Gabriel Balaguer Prunés, Francesc Macrae, Finlay Winship, Ingrid M. Thomas, Huw Evans, Dafydd Gareth Burn, John Greenblatt, Marc de Vos tot Nederveen Cappel, Wouter H. Sijmons, Rolf H. Nielsen, Maartje Bertario, Lucio Bonanni, Bernardo Tibiletti, Maria Grazia Cavestro, Giulia Martina Lindblom, Annika Della Valle, Adriana Lopez Kostner, Francisco Alvarez, Karin Gluck, Nathan Katz, Lior Heinimann, Karl Piñero, Tamara Alejandra Pavicic, Walter Hernan |
| author |
Dominguez Valentin, Mev |
| author_facet |
Dominguez Valentin, Mev Plazzer, John Paul Sampson, Julian R. Engel, Christoph Aretz, Stefan Jenkins, Mark A. Sunde, Lone Bernstein, Inge Capella, Gabriel Balaguer Prunés, Francesc Macrae, Finlay Winship, Ingrid M. Thomas, Huw Evans, Dafydd Gareth Burn, John Greenblatt, Marc de Vos tot Nederveen Cappel, Wouter H. Sijmons, Rolf H. Nielsen, Maartje Bertario, Lucio Bonanni, Bernardo Tibiletti, Maria Grazia Cavestro, Giulia Martina Lindblom, Annika Della Valle, Adriana Lopez Kostner, Francisco Alvarez, Karin Gluck, Nathan Katz, Lior Heinimann, Karl Piñero, Tamara Alejandra Pavicic, Walter Hernan |
| author_role |
author |
| author2 |
Plazzer, John Paul Sampson, Julian R. Engel, Christoph Aretz, Stefan Jenkins, Mark A. Sunde, Lone Bernstein, Inge Capella, Gabriel Balaguer Prunés, Francesc Macrae, Finlay Winship, Ingrid M. Thomas, Huw Evans, Dafydd Gareth Burn, John Greenblatt, Marc de Vos tot Nederveen Cappel, Wouter H. Sijmons, Rolf H. Nielsen, Maartje Bertario, Lucio Bonanni, Bernardo Tibiletti, Maria Grazia Cavestro, Giulia Martina Lindblom, Annika Della Valle, Adriana Lopez Kostner, Francisco Alvarez, Karin Gluck, Nathan Katz, Lior Heinimann, Karl Piñero, Tamara Alejandra Pavicic, Walter Hernan |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ABERRANT SPLICING CANCER INCIDENCE LYNCH SYNDROME MISSENSE MLH1 MSH2 PENETRANCE TRUNCATING |
| topic |
ABERRANT SPLICING CANCER INCIDENCE LYNCH SYNDROME MISSENSE MLH1 MSH2 PENETRANCE TRUNCATING |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2. Fil: Dominguez Valentin, Mev. St Mark’s Hospital; Reino Unido. The Norwegian Radium Hospital; Noruega. European Hereditary Tumour Group; Reino Unido Fil: Plazzer, John Paul. St Mark’s Hospital; Reino Unido. The Royal Melbourne Hospital; Australia Fil: Sampson, Julian R.. European Hereditary Tumour Group; Reino Unido. Cardiff University; Reino Unido Fil: Engel, Christoph. European Hereditary Tumour Group; Reino Unido. Universitat Leipzig; Alemania Fil: Aretz, Stefan. Universitat Bonn; Alemania Fil: Jenkins, Mark A.. University of Melbourne; Australia Fil: Sunde, Lone. Aalborg University; Dinamarca Fil: Bernstein, Inge. Aalborg University; Dinamarca Fil: Capella, Gabriel. European Hereditary Tumour Group; Reino Unido. St Mark’s Hospital; Reino Unido. Institut Català d’Oncologia; España Fil: Balaguer Prunés, Francesc. Universidad de Barcelona; España Fil: Macrae, Finlay. European Hereditary Tumour Group; Reino Unido. The Royal Melbourne Hospital; Australia Fil: Winship, Ingrid M.. University of Melbourne; Australia Fil: Thomas, Huw. Imperial College London; Reino Unido Fil: Evans, Dafydd Gareth. University of Manchester; Reino Unido Fil: Burn, John. Universidad de Newcastle; Australia. The Royal Melbourne Hospital; Australia. St Mark’s Hospital; Reino Unido Fil: Greenblatt, Marc. University of Vermont; Estados Unidos Fil: de Vos tot Nederveen Cappel, Wouter H.. Isala Clinics; Países Bajos Fil: Sijmons, Rolf H.. University of Groningen; Países Bajos. St Mark’s Hospital; Reino Unido. European Hereditary Tumour Group; Reino Unido Fil: Nielsen, Maartje. Leids Universitair Medisch Centrum; Países Bajos Fil: Bertario, Lucio. Fondazione IRCCS Istituto Nazionale dei Tumori; Italia Fil: Bonanni, Bernardo. Fondazione IRCCS Istituto Nazionale dei Tumori; Italia Fil: Tibiletti, Maria Grazia. Università dell’Insubria; Italia Fil: Cavestro, Giulia Martina. Vita-Salute San Raffaele University; Italia Fil: Lindblom, Annika. Karolinska Huddinge Hospital; Suecia Fil: Della Valle, Adriana. Hospital Fuerzas Armadas; Uruguay Fil: Lopez Kostner, Francisco. Clínica Universidad de los Andes; Chile Fil: Alvarez, Karin. Clínica Universidad de los Andes; Chile Fil: Gluck, Nathan. Universitat Tel Aviv; Israel Fil: Katz, Lior. Sheba Medical Center; Israel Fil: Heinimann, Karl. University Hospital Basel; Suiza Fil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina |
| description |
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-06 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/211951 Dominguez Valentin, Mev; Plazzer, John Paul; Sampson, Julian R.; Engel, Christoph; Aretz, Stefan; et al.; No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study; Multidisciplinary Digital Publishing Institute; Journal of Clinical Medicine; 10; 13; 6-2021; 1-12 2077-0383 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/211951 |
| identifier_str_mv |
Dominguez Valentin, Mev; Plazzer, John Paul; Sampson, Julian R.; Engel, Christoph; Aretz, Stefan; et al.; No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study; Multidisciplinary Digital Publishing Institute; Journal of Clinical Medicine; 10; 13; 6-2021; 1-12 2077-0383 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2077-0383/10/13/2856 info:eu-repo/semantics/altIdentifier/doi/10.3390/jcm10132856 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by/2.5/ar/ |
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application/pdf application/pdf application/pdf |
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Multidisciplinary Digital Publishing Institute |
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Multidisciplinary Digital Publishing Institute |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.22299 |