{"id":13982,"date":"2020-08-17T09:31:35","date_gmt":"2020-08-17T07:31:35","guid":{"rendered":"https:\/\/idibell.cat\/?p=13982"},"modified":"2020-08-17T09:39:42","modified_gmt":"2020-08-17T07:39:42","slug":"determinen-la-prevalenca-de-mutacions-en-dues-polimerases-en-pacients-amb-cancer-hereditari","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2020\/08\/determinen-la-prevalenca-de-mutacions-en-dues-polimerases-en-pacients-amb-cancer-hereditari\/","title":{"rendered":"Determinen la prevalen\u00e7a de mutacions en dues polimerases en pacients amb c\u00e0ncer hereditari"},"content":{"rendered":"<p>Algunes de les <strong>ADN polimerases<\/strong>, els enzims encarregats de replicar l&#8217;ADN, tenen una regi\u00f3 que s&#8217;encarrega de corregir els errors que comet el mateix enzim al realitzar la seva funci\u00f3 de c\u00f2pia del genoma. Quan aquesta regi\u00f3 correctora es veu afectada, en concret a les <strong>polimerases anomenades POLE i POLD1<\/strong>, augmenta molt el risc de patir c\u00e0ncer, especialment c\u00e0ncer colorectal. Aix\u00f2 \u00e9s degut al fet que la manca de correcci\u00f3 comporta l&#8217;acumulaci\u00f3 de mutacions en certs teixits que poden provocar el desenvolupament d&#8217;un tumor.<\/p>\n<p>Des que el 2013 es va descriure que les mutacions en el domini corrector de POLE i POLD1 podien promoure l&#8217;aparici\u00f3 de tumors colorectals, s&#8217;han descrit diverses fam\u00edlies de c\u00e0ncer de c\u00f2lon i poliposi que presentaven aquest tipus de mutaci\u00f3. No obstant aix\u00f2, el predomini d&#8217;aquestes mutacions i l&#8217;afectaci\u00f3 d&#8217;altres teixits encara \u00e9s desconegut.<\/p>\n<p>Un equip de l&#8217;Institut de Recerca Biom\u00e8dica de Bellvitge (<a href=\"https:\/\/idibell.cat\/recerca\/area-de-cancer\/programa-de-mecanismes-molleculars-i-terapia-experimental-en-oncologia-oncobell\/cancer-hereditari\/\">IDIBELL<\/a>), l&#8217;Institut Catal\u00e0 d&#8217;Oncologia (<a href=\"http:\/\/ico.gencat.cat\/ca\/inici\">ICO<\/a>) i <a href=\"https:\/\/www.ciberonc.es\/\">CIBERONC<\/a>, liderat per la Dra. Laura Valle i la Dra. Conxi L\u00e1zaro, ha estudiat m\u00e9s de 2.800 pacients de c\u00e0ncer familiar per determinar la prevalen\u00e7a real de les mutacions en les regions correctores de la polimerasa POLE i POLD1.<\/p>\n<p>Els resultats, publicats a la revista <strong><em>Genetics in Medicine<\/em><\/strong>, la revista oficial del <em>American College of Medical Genetics and Genomica<\/em> (ACMG), van mostrar que entre el 0,1 i el 0,4% dels c\u00e0ncers familiars s\u00f3n deguts a mutacions en aquestes regions, i malgrat que <strong>els tumors colorectals s\u00f3n els m\u00e9s abundants tamb\u00e9 es troben en tumors d&#8217;endometri o d&#8217;ovari<\/strong>. Tot i que es tracta d&#8217;una s\u00edndrome minoritari, \u00e9s un gen d&#8217;alt risc, \u00e9s a dir, presentar aquestes mutacions vol dir tenir moltes possibilitats de desenvolupar c\u00e0ncer.<\/p>\n<blockquote><p>&#8220;definir de manera inequ\u00edvoca l&#8217;efecte patog\u00e8nic d&#8217;una variant \u00e9s crucial per al seguiment cl\u00ednic dels portadors, ja que el seu risc a desenvolupar c\u00e0ncer ser\u00e0 alt&#8221; Laura Valle<\/p><\/blockquote>\n<p>A m\u00e9s d&#8217;avaluar la seva prevalen\u00e7a, l&#8217;estudi en profunditat de les variants identificades ha perm\u00e8s definir criteris espec\u00edfics per a la <strong>classificaci\u00f3 de variants en els gens POLE i POLD1<\/strong>, el que permet definir amb m\u00e9s precisi\u00f3 quines variants s\u00f3n patog\u00e8niques, quines no, i les que encara no es pot definir el seu efecte. La Dra. Laura Valle assegura que &#8220;aquestes recomanacions per a la classificaci\u00f3 de variants poden tenir un impacte rellevant en l&#8217;\u00e0mbit cl\u00ednic&#8221;, ja que, &#8220;definir de manera inequ\u00edvoca l&#8217;efecte patog\u00e8nic d&#8217;una variant \u00e9s crucial per al seguiment cl\u00ednic dels portadors, ja que el seu risc a desenvolupar c\u00e0ncer ser\u00e0 alt&#8221;. D&#8217;altra banda, els pacients que presenten aquestes variants i desenvolupen c\u00e0ncer solen ser bons candidats per a la immunoter\u00e0pia, per tant, definir si la variant identificada \u00e9s patog\u00e8nica o no, ser\u00e0 \u00fatil per escollir un tipus de tractament determinat.<\/p>\n<p>&nbsp;<\/p>\n<h3>Un treball d&#8217;equip<\/h3>\n<p>El diagn\u00f2stic gen\u00e8tic dels pacients amb c\u00e0ncer familiar es realitza actualment mitjan\u00e7ant la seq\u00fcenciaci\u00f3 d&#8217;un panell de gens que inclou aquells que quan estan alterats incrementen el risc de patir c\u00e0ncer. En aquest estudi s&#8217;ha extret d&#8217;aquests panells la informaci\u00f3 de la seq\u00fc\u00e8ncia de POLE i POLD1, especialment del domini corrector, de m\u00e9s de 2.800 pacients amb sospita de c\u00e0ncer hereditari. Aquesta an\u00e0lisi s&#8217;ha realitzat a la <strong>Unitat de Diagn\u00f2stic Molecular de l&#8217;ICO<\/strong> (Conxi L\u00e1zaro), on s&#8217;estudien pacients dels diversos centres ICO de Catalunya, aix\u00ed com pacients d&#8217;altres centres del nostre entorn com la Vall d&#8217;Hebron-Institut d&#8217;Oncologia (VHIO), Hospital de la Santa Creu i Sant Pau, Hospital Universitari Parc Taul\u00ed, Consorci Sanitari de Terrassa i Althaia-Manresa).<\/p>\n<p>A m\u00e9s dels membres del Grup de C\u00e0ncer Hereditari de l&#8217;IDIBELL i de l&#8217;ICO, els investigadors han comptat amb la col\u00b7laboraci\u00f3 d&#8217;altres grups d&#8217;aquests centres, com s\u00f3n el Programa d&#8217;Anal\u00edtica de Dades en Oncologia (Dra. Rebeca Sanz-Pamplona i Dr. Victor Moreno ) i el servei d&#8217;Oncologia (Dr. Josep M. Piulats). Tamb\u00e9 s&#8217;ha comptat amb la participaci\u00f3 del servei d&#8217;Anatomia Patol\u00f2gica de l&#8217;Hospital Universitari de Bellvitge (Dr. August Vidal i Dr. Xavier Mat\u00edas-Guiu), del grup de la Dra. Rosa Aligu\u00e9 de la Facultat de Medicina de la Universitat de Barcelona (UB), IDIBAPS, i del Dr. Tirso Pons, del departament d&#8217;Immunologia i Oncologia del Centre Nacional de Biotecnologia (CNB-CSIC).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Un equip del grup de C\u00e0ncer Hereditari IDIBELL-ICO estudia m\u00e9s de 2.800 pacients amb sospita de c\u00e0ncer hereditari per a determinar la freq\u00fc\u00e8ncia de mutacions patog\u00e8niques a la regi\u00f3 correctora de dues polimerases.<br \/>\nLa identificaci\u00f3 d&#8217;aquestes mutacions pot ajudar al diagn\u00f2stic preco\u00e7 i al tractament personalitzat d&#8217;aquests pacients.<\/p>\n","protected":false},"author":8,"featured_media":13983,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"default","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":"default","adv-header-id-meta":"","stick-header-meta":"default","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":"","background-image":"","background-repeat":"repeat","background-position":"center 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