{"id":8359,"date":"2014-06-03T00:00:00","date_gmt":"2014-06-02T22:00:00","guid":{"rendered":"https:\/\/idibell.cat\/blog\/2014\/06\/03\/caracteritzacio-molecular-de-families-de-cancer-de-colon-hereditari-sense-causa-genetica-identificada\/"},"modified":"2020-05-13T19:48:06","modified_gmt":"2020-05-13T17:48:06","slug":"caracteritzacio-molecular-de-families-de-cancer-de-colon-hereditari-sense-causa-genetica-identificada","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2014\/06\/caracteritzacio-molecular-de-families-de-cancer-de-colon-hereditari-sense-causa-genetica-identificada\/","title":{"rendered":"Caracteritzaci\u00f3 molecular de fam\u00edlies de c\u00e0ncer de c\u00f2lon hereditari sense causa gen\u00e8tica identificada"},"content":{"rendered":"

Durant les \u00faltimes d\u00e8cades, s’ha realitzat un gran esfor\u00e7 per dilucidar les causes gen\u00e8tiques dels casos de c\u00e0ncer colorectal familiar. Tot i aix\u00f2, inclosos els darrers aven\u00e7os tecnol\u00f2gics que han perm\u00e8s estudiar l’exoma o genoma complet dels membres de fam\u00edlies afectades , encara no \u00e9s possible explicar gran part de la predisposici\u00f3 gen\u00e8tica al c\u00e0ncer colorectal. <\/p>\n

En el Programa de C\u00e0ncer Hereditari de l’ICO-IDIBELL la l\u00ednia de treball que dirigeix \u200b\u200bla investigadora Laura Valle Velasco est\u00e0 dedicada a l’estudi molecular de fam\u00edlies d’alt risc en qu\u00e8 encara es desconeix la causa gen\u00e8tica d’aquesta predisposici\u00f3 a desenvolupar c\u00e0ncer de c\u00f2lon i recte. <\/p>\n

Per tal d’identificar nous gens de c\u00e0ncer hereditari s’ha seq\u00fc\u00e8nciat l\u2019exoma complet, \u00e9s a dir la part codificant del genoma, dels membres afectats de c\u00e0ncer d’una d’aquestes fam\u00edlies. La fam\u00edlia estudiada mostrava un patr\u00f3 d’her\u00e8ncia aparentment dominant, i els familiars amb c\u00e0ncer no havien desenvolupat p\u00f2lips al c\u00f2lon. De manera inesperada, es van identificar mutacions en un gen ja conegut de predisposici\u00f3 al c\u00e0ncer colorectal i a poliposi col\u00f2nica que segueix un patr\u00f3 d’her\u00e8ncia recessiu, el gen MUTYH. <\/p>\n

En base als resultats obtinguts en aquest estudi, es proposa una reorientaci\u00f3 del proc\u00e9s de selecci\u00f3 de fam\u00edlies per a l’estudi de MUTYH on es contempla la pres\u00e8ncia d’un patr\u00f3 d’her\u00e8ncia dominant a causa del risc que aporten les mutacions en un s\u00f2l al\u00b7lel, la possibilitat que no hi hagi p\u00f2lips en el moment del diagn\u00f2stic, aix\u00ed com que hi hagi tumors amb trets moleculars caracter\u00edstics d’altres s\u00edndromes de c\u00e0ncer colorectal hereditari com \u00e9s la inestabilitat de microsat\u00e8l\u00b7lits . <\/p>\n

D’altra banda, donant suport a estudis previs, es proposa l’an\u00e0lisi d’una mutaci\u00f3 concreta [KRAS c.34G > T ( p.G12C )], caracter\u00edstica dels tumors associats a MUTYH, com a test de selecci\u00f3 de fam\u00edlies elegibles per a l’estudi del gen en l\u00ednia germinal. <\/p>\n

A m\u00e9s de la implicaci\u00f3 del Programa de C\u00e0ncer Hereditari aquest estudi ha comptat amb la col\u00b7laboraci\u00f3 de grups de la Universitat de Frankfurt (Guido Plotz), de la Universitat d’Oviedo (Xose S. Puente) i del Centre Nacional d’An\u00e0lisi Gen\u00f2mica (CNAG). <\/p>\n

Un altre estudi de l’equip de Valle per caracteritzar les fam\u00edlies amb c\u00e0ncer colorectal hereditari sense causa gen\u00e8tica coneguda, ha realitzat una an\u00e0lisi exhaustiva dels trets moleculars dels tumors desenvolupats en el context del c\u00e0ncer colorectal hereditari no polip\u00f2sic sense alteracions en els gens de reparaci\u00f3 de l’ADN, que causarien la s\u00edndrome de Lynch. <\/p>\n

Per a aix\u00f2, s’han estudiat les alteracions gen\u00f2miques, mutacions en gens rellevants en c\u00e0ncer de c\u00f2lon com s\u00f3n KRAS, BRAF,TP53 i PIK3CA, i el nivell de metilaci\u00f3 global d’illes CpG tant en tumors hereditaris com espor\u00e0dics. Els resultats obtinguts indiquen que aquests tumors hereditaris mostren perfils gen\u00f2mics molt similars als perfils dels tumors espor\u00e0dics, tots dos suggerents d’una alta inestabilitat cromos\u00f2mica i un baix nivell de metilaci\u00f3 d’illes CpG. <\/p>\n

No obstant aix\u00f2, s’han identificat algunes caracter\u00edstiques espec\u00edfiques, com el guany del cromosoma 2, la p\u00e8rdua de 10q o una menor freq\u00fc\u00e8ncia de mutacions en TP53, que podrien ser rellevants per al maneig cl\u00ednic d’aquests pacients o per a la identificaci\u00f3 dels defectes en l\u00ednia germinal causants de l’agregaci\u00f3 de c\u00e0ncer en aquestes fam\u00edlies. Per a aquest projecte el Programa de C\u00e0ncer Hereditari ha comptat amb la col\u00b7laboraci\u00f3 d’altres grups de l’ICO-IDIBELL (Unitat de Biomarcadors i Susceptibilitat i Laboratori de Recerca Translacional). <\/p>\n

Nuria Segu\u00ed, Matilde Navarro, Marta Pineda, Nicole K\u00f6ger, Fernando Bellido, Sara Gonz\u00e1lez, Olga Campos, Silvia Iglesias, Rafael Vald\u00e9s-Mas, Adriana L\u00f3pez-Doriga, Marta Gut, Ignacio Blanco, Conxi L\u00e1zaro, Gabriel Capell\u00e1, Xose S. Puente, *Guido Plotz, *Laura Valle. Exome sequencing identifies MUTYH mutations in a family with colorectal cancer and an atypical phenotype.<\/a> Gut 2014 [Epub ahead of print] <\/p>\n

Fernando Bellido, Marta Pineda, Rebeca Sanz-Pamplona, Matilde Navarro, Marga Nadal, Conxi L\u00e1zaro, Ignacio Blanco, Victor Moreno, Gabriel Capell\u00e1, Laura Valle. Comprehensive molecular characterisation of hereditary non-polyposis colorectal tumours with mismatch repair proficiency. European Journal of Cancer 2014 [Epub ahead of print]<\/p>\n","protected":false},"excerpt":{"rendered":"

Durant les \u00faltimes d\u00e8cades, s’ha realitzat un gran esfor\u00e7 per dilucidar les causes gen\u00e8tiques dels casos de c\u00e0ncer colorectal familiar. Tot i aix\u00f2, inclosos els darrers aven\u00e7os tecnol\u00f2gics que han perm\u00e8s estudiar l’exoma o genoma complet dels membres de fam\u00edlies afectades , encara no \u00e9s possible explicar gran part de la predisposici\u00f3 gen\u00e8tica al c\u00e0ncer […]<\/p>\n","protected":false},"author":6,"featured_media":11007,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","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 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":[1],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-25 06:32:00","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8359"}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=8359"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8359\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/11007"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=8359"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=8359"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=8359"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}