A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome

Autores
Mampel, Alejandra; Cambados, N.; Valdemoros, Paula; Vargas, Ana Lía; Hidalgo, J.; Nadin, Silvina Beatriz
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Lynch syndrome (LS) is the most common cause of hereditary colon cancer which predisposen to colorectal, endometrial, and other cancers. LS is caused by germline mutations in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). The MMR system detects and corrects replication errors, maintaining the stability of the genome. Consequently defects in the MMR increase the mutation rate causes microsatellite instability (MSI) and increased cancer risk. The main objective of our study was to analyze clinical characteristics and diagnostic algorithms of two unrelated families from Mendoza, Argentina, carrying a specific mutation in MLH1 gene. The clinical importance of these mutations and their significance in the general population were also examined. After carrying out the genealogical study, MMR proteins MLH1, MSH2, MSH6 and PMS2 were evaluated in paraffin-embedded tissue sections from colorectal tumors using Ventana Benchmark automated immunostaining. MSI analysis was performed using STRs markers (NR-21, NR-24, BAT-25, BAT-26 and Mono-27) and Illumina next-generation sequencing (NGS). Family characteristics and evidences are presented below. Family A: a male patient, 36 years old, with right-sided colon cancer and MLH1/PMS2 proteins absent by immunohistochemistry (IHC). Two sisters with colorectal cancer before 40 years of age. The father and the paternal grandmother died from colon cancer. A pathogenic mutation was localized in MLH1 c.1890dupT (p.Asp631Ter1) by NGS. Family B: a 33-year-old male patient with right-sided colon cancer. IHC staining showed the absence of MLH1 expression. The patient also presented MSI. The mother had endometrial and colon cancer, a maternal uncle had colon cancer and papillary urothelial carcinoma, and the maternal grandfather had colon cancer. Using NGS, a mutation in MLH1 c.1890dupT (p.Asp631Ter1) was found. Our results demonstrate the important implications of clinical and molecular algorithms to improve the efficiency of LS diagnosis, as well as the detection of asymptomatic carriers. These data allow to established guidelines for the follow-up, risk-reduction management and treatment strategies for patients found to has pathogenic mutations. In addition, our data contribute to determine frequencies of specific mutations in the general population. The mutation of the MLH1 gene described above is prevalent among families with LS in South America.
Fil: Mampel, Alejandra. Universidad Nacional de Cuyo. Hospital Universitario; Argentina
Fil: Cambados, N.. Hospital Perrupato. Servicio de Anatomía Patológicas y Citología; Argentina
Fil: Valdemoros, Paula. Héritas; Argentina
Fil: Vargas, Ana Lía. Universidad Nacional de Cuyo. Hospital Universitario; Argentina
Fil: Hidalgo, J.. Universidad Nacional de Cuyo. Hospital Universitario; Argentina
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo
Mendoza
Argentina
Sociedad de Biología de Cuyo
Materia
DNA DAMAGE
CISPLATIN
CANCER
HSP27
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/212422
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/212422
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A specific MLH1 gene mutation in families from Mendoza associated with lynch syndromeMampel, AlejandraCambados, N.Valdemoros, PaulaVargas, Ana LíaHidalgo, J.Nadin, Silvina BeatrizDNA DAMAGECISPLATINCANCERHSP27https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Lynch syndrome (LS) is the most common cause of hereditary colon cancer which predisposen to colorectal, endometrial, and other cancers. LS is caused by germline mutations in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). The MMR system detects and corrects replication errors, maintaining the stability of the genome. Consequently defects in the MMR increase the mutation rate causes microsatellite instability (MSI) and increased cancer risk. The main objective of our study was to analyze clinical characteristics and diagnostic algorithms of two unrelated families from Mendoza, Argentina, carrying a specific mutation in MLH1 gene. The clinical importance of these mutations and their significance in the general population were also examined. After carrying out the genealogical study, MMR proteins MLH1, MSH2, MSH6 and PMS2 were evaluated in paraffin-embedded tissue sections from colorectal tumors using Ventana Benchmark automated immunostaining. MSI analysis was performed using STRs markers (NR-21, NR-24, BAT-25, BAT-26 and Mono-27) and Illumina next-generation sequencing (NGS). Family characteristics and evidences are presented below. Family A: a male patient, 36 years old, with right-sided colon cancer and MLH1/PMS2 proteins absent by immunohistochemistry (IHC). Two sisters with colorectal cancer before 40 years of age. The father and the paternal grandmother died from colon cancer. A pathogenic mutation was localized in MLH1 c.1890dupT (p.Asp631Ter1) by NGS. Family B: a 33-year-old male patient with right-sided colon cancer. IHC staining showed the absence of MLH1 expression. The patient also presented MSI. The mother had endometrial and colon cancer, a maternal uncle had colon cancer and papillary urothelial carcinoma, and the maternal grandfather had colon cancer. Using NGS, a mutation in MLH1 c.1890dupT (p.Asp631Ter1) was found. Our results demonstrate the important implications of clinical and molecular algorithms to improve the efficiency of LS diagnosis, as well as the detection of asymptomatic carriers. These data allow to established guidelines for the follow-up, risk-reduction management and treatment strategies for patients found to has pathogenic mutations. In addition, our data contribute to determine frequencies of specific mutations in the general population. The mutation of the MLH1 gene described above is prevalent among families with LS in South America.Fil: Mampel, Alejandra. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Cambados, N.. Hospital Perrupato. Servicio de Anatomía Patológicas y Citología; ArgentinaFil: Valdemoros, Paula. Héritas; ArgentinaFil: Vargas, Ana Lía. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Hidalgo, J.. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaXXXVI Reunión Científica Anual de la Sociedad de Biología de CuyoMendozaArgentinaSociedad de Biología de CuyoTech Science Press2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212422A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome; XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; Mendoza; Argentina; 2018; 30-300327-95451667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://sbcuyo.org.ar/wp-content/uploads/2019/08/Biocell-2018.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:02:20Zoai:ri.conicet.gov.ar:11336/212422instacron: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:34982025-09-10 13:02:20.864CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
title A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
spellingShingle A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
Mampel, Alejandra
DNA DAMAGE
CISPLATIN
CANCER
HSP27
title_short A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
title_full A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
title_fullStr A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
title_full_unstemmed A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
title_sort A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome
dc.creator.none.fl_str_mv Mampel, Alejandra
Cambados, N.
Valdemoros, Paula
Vargas, Ana Lía
Hidalgo, J.
Nadin, Silvina Beatriz
author Mampel, Alejandra
author_facet Mampel, Alejandra
Cambados, N.
Valdemoros, Paula
Vargas, Ana Lía
Hidalgo, J.
Nadin, Silvina Beatriz
author_role author
author2 Cambados, N.
Valdemoros, Paula
Vargas, Ana Lía
Hidalgo, J.
Nadin, Silvina Beatriz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DNA DAMAGE
CISPLATIN
CANCER
HSP27
topic DNA DAMAGE
CISPLATIN
CANCER
HSP27
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Lynch syndrome (LS) is the most common cause of hereditary colon cancer which predisposen to colorectal, endometrial, and other cancers. LS is caused by germline mutations in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). The MMR system detects and corrects replication errors, maintaining the stability of the genome. Consequently defects in the MMR increase the mutation rate causes microsatellite instability (MSI) and increased cancer risk. The main objective of our study was to analyze clinical characteristics and diagnostic algorithms of two unrelated families from Mendoza, Argentina, carrying a specific mutation in MLH1 gene. The clinical importance of these mutations and their significance in the general population were also examined. After carrying out the genealogical study, MMR proteins MLH1, MSH2, MSH6 and PMS2 were evaluated in paraffin-embedded tissue sections from colorectal tumors using Ventana Benchmark automated immunostaining. MSI analysis was performed using STRs markers (NR-21, NR-24, BAT-25, BAT-26 and Mono-27) and Illumina next-generation sequencing (NGS). Family characteristics and evidences are presented below. Family A: a male patient, 36 years old, with right-sided colon cancer and MLH1/PMS2 proteins absent by immunohistochemistry (IHC). Two sisters with colorectal cancer before 40 years of age. The father and the paternal grandmother died from colon cancer. A pathogenic mutation was localized in MLH1 c.1890dupT (p.Asp631Ter1) by NGS. Family B: a 33-year-old male patient with right-sided colon cancer. IHC staining showed the absence of MLH1 expression. The patient also presented MSI. The mother had endometrial and colon cancer, a maternal uncle had colon cancer and papillary urothelial carcinoma, and the maternal grandfather had colon cancer. Using NGS, a mutation in MLH1 c.1890dupT (p.Asp631Ter1) was found. Our results demonstrate the important implications of clinical and molecular algorithms to improve the efficiency of LS diagnosis, as well as the detection of asymptomatic carriers. These data allow to established guidelines for the follow-up, risk-reduction management and treatment strategies for patients found to has pathogenic mutations. In addition, our data contribute to determine frequencies of specific mutations in the general population. The mutation of the MLH1 gene described above is prevalent among families with LS in South America.
Fil: Mampel, Alejandra. Universidad Nacional de Cuyo. Hospital Universitario; Argentina
Fil: Cambados, N.. Hospital Perrupato. Servicio de Anatomía Patológicas y Citología; Argentina
Fil: Valdemoros, Paula. Héritas; Argentina
Fil: Vargas, Ana Lía. Universidad Nacional de Cuyo. Hospital Universitario; Argentina
Fil: Hidalgo, J.. Universidad Nacional de Cuyo. Hospital Universitario; Argentina
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo
Mendoza
Argentina
Sociedad de Biología de Cuyo
description Lynch syndrome (LS) is the most common cause of hereditary colon cancer which predisposen to colorectal, endometrial, and other cancers. LS is caused by germline mutations in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). The MMR system detects and corrects replication errors, maintaining the stability of the genome. Consequently defects in the MMR increase the mutation rate causes microsatellite instability (MSI) and increased cancer risk. The main objective of our study was to analyze clinical characteristics and diagnostic algorithms of two unrelated families from Mendoza, Argentina, carrying a specific mutation in MLH1 gene. The clinical importance of these mutations and their significance in the general population were also examined. After carrying out the genealogical study, MMR proteins MLH1, MSH2, MSH6 and PMS2 were evaluated in paraffin-embedded tissue sections from colorectal tumors using Ventana Benchmark automated immunostaining. MSI analysis was performed using STRs markers (NR-21, NR-24, BAT-25, BAT-26 and Mono-27) and Illumina next-generation sequencing (NGS). Family characteristics and evidences are presented below. Family A: a male patient, 36 years old, with right-sided colon cancer and MLH1/PMS2 proteins absent by immunohistochemistry (IHC). Two sisters with colorectal cancer before 40 years of age. The father and the paternal grandmother died from colon cancer. A pathogenic mutation was localized in MLH1 c.1890dupT (p.Asp631Ter1) by NGS. Family B: a 33-year-old male patient with right-sided colon cancer. IHC staining showed the absence of MLH1 expression. The patient also presented MSI. The mother had endometrial and colon cancer, a maternal uncle had colon cancer and papillary urothelial carcinoma, and the maternal grandfather had colon cancer. Using NGS, a mutation in MLH1 c.1890dupT (p.Asp631Ter1) was found. Our results demonstrate the important implications of clinical and molecular algorithms to improve the efficiency of LS diagnosis, as well as the detection of asymptomatic carriers. These data allow to established guidelines for the follow-up, risk-reduction management and treatment strategies for patients found to has pathogenic mutations. In addition, our data contribute to determine frequencies of specific mutations in the general population. The mutation of the MLH1 gene described above is prevalent among families with LS in South America.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/212422
A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome; XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; Mendoza; Argentina; 2018; 30-30
0327-9545
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/212422
identifier_str_mv A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome; XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; Mendoza; Argentina; 2018; 30-30
0327-9545
1667-5746
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://sbcuyo.org.ar/wp-content/uploads/2019/08/Biocell-2018.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Tech Science Press
publisher.none.fl_str_mv Tech Science Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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