{"id":116565,"date":"2018-03-11T10:45:46","date_gmt":"2018-03-11T10:45:46","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/caracterizacion-molecular-y-prevalencia-de-las-variantes-geneticas-en-brca1-2-en-el-sa%c2%adndrome-de-cancer-de-mama-y-ovario-hereditario-en-la-region-de-murcia\/"},"modified":"2018-03-11T10:45:46","modified_gmt":"2018-03-11T10:45:46","slug":"caracterizacion-molecular-y-prevalencia-de-las-variantes-geneticas-en-brca1-2-en-el-sa%c2%adndrome-de-cancer-de-mama-y-ovario-hereditario-en-la-region-de-murcia","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/oncologia-clinica\/caracterizacion-molecular-y-prevalencia-de-las-variantes-geneticas-en-brca1-2-en-el-sa%c2%adndrome-de-cancer-de-mama-y-ovario-hereditario-en-la-region-de-murcia\/","title":{"rendered":"Caracterizaci\u00f3n molecular y preValencia de las variantes gen\u00e9ticas en brca1\/2 en el s\u00edndrome de c\u00e1ncer de mama y ovario hereditario en la regi\u00f3n de murcia"},"content":{"rendered":"

Tesis doctoral de Xavier Gabaldo Barrios <\/strong><\/h2>\n

Resumen: el c\u00e1ncer de mama es la principal causa de mortalidad por c\u00e1ncer en las mujeres en todo el mundo, con una estimaci\u00f3n de 1,68 millones de nuevos casos y m\u00e1s de 521.000 muertes s\u00f3lo en 2012. Las mujeres con una historia familiar de c\u00e1ncer de mama tienen de 1,5 a 3,9 veces m\u00e1s probabilidades de desarrollar c\u00e1ncer de mama que las mujeres sin antecedentes familiares, en funci\u00f3n del n\u00famero y grado de parentesco de los miembros de la familia afectados. Aunque esta asociaci\u00f3n podr\u00eda surgir a causa del entorno compartido y estilo de vida, tambi\u00e9n puede ser debido a la susceptibilidad gen\u00e9tica heredada. Los genes con mayor penetrancia y preValencia en el s\u00edndrome de c\u00e1ncer de mama y ovario hereditario (cmoh) son brca1 y brca2, los cuales explican el 20% de este s\u00edndrome. Se ha realizado una caracterizaci\u00f3n molecular y un an\u00e1lisis de preValencia de las variantes encontradas de brca1 y brca2 en 396 familias de riesgo de cmoh de la regi\u00f3n de murcia. Para la secuenciaci\u00f3n de exones y zonas colindantes de brca1 y brca2 hemos empleado el m\u00e9todo de modificaci\u00f3n de sanger por secuenciaci\u00f3n autom\u00e1tica de electroforesis capilar y la pirosecuenciaci\u00f3n (gs junior 454, roche diagnostics). El screening de los reordenamientos gen\u00e9ticos se realiz\u00f3 por tecnolog\u00eda mlpa. Para la comprobaci\u00f3n de los reordenamientos detectados utilizamos la tecnolog\u00eda de pcr a tiempo real y para demostrar el efecto fundador de las variantes patog\u00e9nicas de nueva descripci\u00f3n con m\u00e1s de una familia no relacionada se realiz\u00f3 an\u00e1lisis de microsat\u00e9lites. El 17,7% de las familias es portadora de alguna variante patog\u00e9nica en brca1\/2 y el 11,49% fueron variantes de significado cl\u00ednico desconocido. Siete variantes patog\u00e9nicas fueron de nueva descripci\u00f3n, de las cuales c.1918c>t (brca1) proviene de un ancestro com\u00fan en nuestra regi\u00f3n. Se han identificado variantes de efecto cl\u00ednico desconocido de mayor probabilidad pat\u00f3gena seg\u00fan estudios in silico. Las variantes de efecto cl\u00ednico desconocido missense de mayor probabilidad pat\u00f3gena han resultado ser c.946a>g (brca1), c.3032c>g (brca2), c.7559g>t (brca2) y c.9875c>t (brca2); mientras que las variantes splicing de mayor probabilidad pat\u00f3gena han sido c.68-7t>a (brca2), c.7008-14delt (brca2) y c.4501+3a>t (brca2). Los pacientes portadores de una variante patog\u00e9nica en brca1\/2 tienen mayor riesgo de tener un c\u00e1ncer bilateral de mama y c\u00e1ncer de mama en var\u00f3n que en el resto de pacientes brcax. Existe asociaci\u00f3n entre los pacientes brca1+ y los c\u00e1nceres de mama triple negativo, con mayor presentaci\u00f3n del tipo histol\u00f3gico medular. Los c\u00e1nceres de ovario brca1\/2+ suelen ser de tipo histol\u00f3gico seroso y existe una mayor preValencia de este tipo de c\u00e1ncer en brca1 con respecto a brca2 en nuestro estudio (33% vs. 16,7%, respectivamente). abstract: breast cancer is the leading cause of cancer death in women worldwide, with an estimated 1.68 million new cases and 521,000 deaths in 2012. Women with a family history of breast cancer are 1.5 to 3.9-fold more likely to develop breast cancer than women without a family history, depending on the number and degree of kinship of the affected family members. Although this association could arise because of the shared environment and lifestyle, it can also be due to inherited genetic susceptibility. Brca1 and brca2 are genes with greater penetrance and prevalence in hereditary breast and ovarian cancer (hboc), but account 20% of these cancers. In this study we performed a molecular characterization and analysis of prevalence of brca1 and brca2 mutations in 396 families at risk of hboc in the region of murcia. For sequencing of exons and adjacent areas of brca1 and brca2 genes, we used the method of modification of sanger sequencing by automated capillary electrophoresis and pyrosequencing (junior gs 454, roche diagnostics). The screening of gene rearrangements was performed by mlpa technology. For the verification of detected rearrangements we used real-time pcr and to demonstrate founder effect of novel pathogenic variants with more than one unrelated family, microsatellite analysis was performed. The 17.7% of families are carriers of a pathogenic variant in brca1\/2 and 11.49% are unknown variants. Seven pathogenic variants were novel, which c.1918c> t (brca1) comes from a common ancestor in our region. Have been identified unknown variants of increased pathogenic probability according to in silico tools. Missense variants of unknown clinical effect likely pathogenic were c.946a>g (brca1), c.3032c>g (brca2), c.7559g>t (brca2) and c.9875c>t (brca2); while splicing variants likely pathogenic were c.68-7t>a (brca2), c.7008-14delt (brca2) and c.4501+3a>t (brca2). Brca1\/2 carriers are at increased risk of having a bilateral breast cancer and male breast cancer than patients brcax. There is an association between brca1+ patients and triple negative breast cancers with medullary histological type overpresentation. Ovarian cancer brca1\/2+ are usually serous histological type and there is a higher prevalence of this type of cancer in brca1 regarding brca2 (33% versus 16.7%, respectively).<\/p>\n

 <\/p>\n

Datos acad\u00e9micos de la tesis doctoral \u00abCaracterizaci\u00f3n molecular y preValencia de las variantes gen\u00e9ticas en brca1\/2 en el s\u00edndrome de c\u00e1ncer de mama y ovario hereditario en la regi\u00f3n de murcia<\/strong>\u00ab<\/h3>\n
    \n
  • T\u00edtulo de la tesis:<\/strong>\u00a0 Caracterizaci\u00f3n molecular y preValencia de las variantes gen\u00e9ticas en brca1\/2 en el s\u00edndrome de c\u00e1ncer de mama y ovario hereditario en la regi\u00f3n de murcia <\/li>\n
  • Autor:<\/strong>\u00a0 Xavier Gabaldo Barrios <\/li>\n
  • Universidad:<\/strong>\u00a0 Murcia<\/li>\n
  • Fecha de lectura de la tesis:<\/strong>\u00a0 31\/10\/2014<\/li>\n<\/ul>\n

     <\/p>\n

    Direcci\u00f3n y tribunal<\/h3>\n
      \n
    • Director de la tesis<\/strong>\n
        \n
      • Francisco Ruiz Espejo<\/li>\n<\/ul>\n<\/li>\n
      • Tribunal<\/strong>\n
          \n
        • Presidente del tribunal: anibal Nieto diaz <\/li>\n
        • Jos\u00e9 Antonio Noguera velasco (vocal)<\/li>\n
        • pedro Perez segura (vocal)<\/li>\n
        • isabel Tovar zapata (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n

           <\/p>\n","protected":false},"excerpt":{"rendered":"

          Tesis doctoral de Xavier Gabaldo Barrios Resumen: el c\u00e1ncer de mama es la principal causa de mortalidad por c\u00e1ncer en […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[36483,8235,347],"tags":[154731,77547,25063,224729,70550,230066],"class_list":["post-116565","post","type-post","status-publish","format-standard","hentry","category-biologia-molecular","category-murcia","category-oncologia-clinica","tag-anibal-nieto-diaz","tag-francisco-ruiz-espejo","tag-isabel-tovar-zapata","tag-jose-antonio-noguera-velasco","tag-pedro-perez-segura","tag-xavier-gabaldo-barrios"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/116565","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=116565"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/116565\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=116565"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=116565"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=116565"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}