{"id":19837,"date":"2022-09-15T11:59:00","date_gmt":"2022-09-15T14:59:00","guid":{"rendered":"https:\/\/mindthegraph.com\/blog\/?p=19837"},"modified":"2023-03-20T09:54:50","modified_gmt":"2023-03-20T12:54:50","slug":"cutaneous-and-acral-melanoma","status":"publish","type":"post","link":"https:\/\/mindthegraph.com\/blog\/cs\/kozni-a-akralni-melanom\/","title":{"rendered":"P\u0159ehled v\u00fdzkumu: Ko\u017en\u00ed a akr\u00e1ln\u00ed melanom"},"content":{"rendered":"

Ji\u017e n\u011bkolik desetilet\u00ed je v n\u011bkter\u00fdch populac\u00edch celosv\u011btov\u011b zaznamen\u00e1v\u00e1n n\u00e1r\u016fst v\u00fdskytu melanomu. Novotvar melanocyt\u016f v k\u016f\u017ei, sliznici nebo uvey se naz\u00fdv\u00e1 melanom. Navzdory sv\u00e9mu 5% zastoupen\u00ed mezi v\u0161emi ko\u017en\u00edmi malignitami je zodpov\u011bdn\u00fd za v\u00edce ne\u017e 75% v\u0161ech \u00famrt\u00ed na rakovinu k\u016f\u017ee.\u00a0<\/p>\n\n\n\n

A\u010dkoli je pozitivn\u00ed souvislost mezi expozic\u00ed UV z\u00e1\u0159en\u00ed a vznikem melanomu dob\u0159e zn\u00e1m\u00e1, epigenetick\u00e9 mechanismy, kter\u00e9 jsou v pozad\u00ed, nejsou v lidsk\u00fdch melanomov\u00fdch tk\u00e1n\u00edch z velk\u00e9 \u010d\u00e1sti prozkoum\u00e1ny. Tento \u010dl\u00e1nek se bude zab\u00fdvat prognostick\u00fdm n\u00e1dorov\u00fdm faktorem souvisej\u00edc\u00edm s patobiologi\u00ed a expozic\u00ed ultrafialov\u00e9mu z\u00e1\u0159en\u00ed spolu s autorov\u00fdmi post\u0159ehy na v\u00fd\u0161e uveden\u00e9 t\u00e9ma. <\/p>\n\n\n\n

C\u00edl studie<\/h2>\n\n\n\n

Na dvou nez\u00e1visl\u00fdch kohort\u00e1ch pacient\u016f s ko\u017en\u00edm melanomem se sna\u017e\u00ed objevit a ov\u011b\u0159it metyla\u010dn\u00ed zm\u011bny v cel\u00e9m genomu spojen\u00e9 s UV mutacemi. Kl\u00ed\u010dov\u00fdm c\u00edlem je prozkoumat diagnostick\u00fd potenci\u00e1l metylom\u016f DNA oproti transkriptom\u016fm a integrovan\u00fdm metylom\u016fm-transkriptom\u016fm pro rozli\u0161en\u00ed ko\u017en\u00edch melanom\u016f s UV mutac\u00ed a bez UV mutace. <\/p>\n\n\n\n

Pomoc\u00ed integrativn\u00edho p\u0159\u00edstupu OMIC se hodnot\u00ed mal\u00e9 nukleotidov\u00e9 varianty (SNV) a varianty po\u010dtu kopi\u00ed (CNV) prioritn\u00edch diferenci\u00e1ln\u011b metylovan\u00fdch gen\u016f z hlediska potenci\u00e1lu n\u00e1dorov\u00fdch faktor\u016f. Tento v\u00fdzkum je d\u00e1le podpo\u0159en dal\u0161\u00edm, kter\u00fd zkoum\u00e1, zda metylomy DNA mohou rozli\u0161it patologick\u00e9 a s UV z\u00e1\u0159en\u00edm souvisej\u00edc\u00ed rozd\u00edly mezi prominentn\u00edmi variantami melanomu, kter\u00e9 jsou spojeny s expozic\u00ed UV z\u00e1\u0159en\u00ed (ko\u017en\u00ed melanom), a t\u011bmi, kter\u00e9 nejsou (akr\u00e1ln\u00ed melanom). Sch\u00e9ma v \u010dl\u00e1nku ukazuje, jak\u00fd je c\u00edl a postup studie. Grafick\u00e9 zn\u00e1zorn\u011bn\u00ed bylo vytvo\u0159eno pomoc\u00ed Mind the Graph<\/a><\/strong>.<\/p>\n\n\n\n

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Podrobn\u00e9 posouzen\u00ed studie<\/h2>\n\n\n\n

V klinick\u00fdch bioptick\u00fdch vzorc\u00edch bylo UV z\u00e1\u0159en\u00ed (UV) spojeno s ko\u017en\u00edm melanomem, ale epigenetick\u00e9 mechanismy, kter\u00e9 jsou z\u00e1kladem t\u011bchto mechanism\u016f, dosud nebyly stanoveny. Do t\u00e9to studie byla zahrnuta multietnick\u00e1 kohorta 112 ko\u017en\u00edch melanom\u016f pro klinick\u00e9, epigenomov\u00e9 (DNA metylom), genomov\u00e9 a transkriptomov\u00e9 profilov\u00e1n\u00ed. V t\u00e9to studii identifikuj\u00ed UV z\u00e1\u0159en\u00edm indukovan\u00e9 zm\u011bny v imunologick\u00fdch a regula\u010dn\u00edch drah\u00e1ch, kter\u00e9 mohou b\u00fdt p\u0159\u00ed\u010dinou vzniku rakoviny nap\u0159\u00ed\u010d multi-OMIC.<\/p>\n\n\n\n

Krom\u011b toho, \u017ee se jedn\u00e1 o nejkriti\u010dt\u011bj\u0161\u00ed gen, je TAPBP (Tap binding protein gene) kriticky zapojen do imunitn\u00edch funkc\u00ed, p\u0159i\u010dem\u017e n\u011bkolik UV zm\u011bn\u011bn\u00fdch metyla\u010dn\u00edch m\u00edst, kter\u00e1 byla ov\u011b\u0159ena c\u00edlen\u00fdm sekvenov\u00e1n\u00edm, poskytuje klinicky vyu\u017eiteln\u00e9 mo\u017enosti. MHC-I interaguje s transport\u00e9rem spojen\u00fdm se zpracov\u00e1n\u00edm antigenu prost\u0159ednictv\u00edm TAPBP, \u010dlena superrodiny imunoglobulin\u016f. \u0158ada n\u00e1dorov\u00fdch onemocn\u011bn\u00ed vykazuje downregulaci proteinu TAPBP (tapasin), kter\u00e1 se obnovuje po p\u016fsoben\u00ed cytokin\u016f.\u00a0<\/p>\n\n\n\n

To nazna\u010duje, \u017ee nedostate\u010dn\u00e1 exprese TAPBP m\u016f\u017ee b\u00fdt zp\u016fsobena sp\u00ed\u0161e dysregulac\u00ed ne\u017e struktur\u00e1ln\u00edmi zm\u011bnami. V\u011bdci zjistili, \u017ee hladiny metylace DNA TAPBP jsou v\u00fdznamn\u011b nep\u0159\u00edmo \u00fam\u011brn\u00e9 transkripci a \u017ee tato je zm\u011bn\u011bna sp\u00ed\u0161e v d\u016fsledku vystaven\u00ed UV z\u00e1\u0159en\u00ed ne\u017e v d\u016fsledku patologick\u00e9 identity melanomu. U ko\u017en\u00edch ani akr\u00e1ln\u00edch melanom\u016f bez UV mutace nebyla zji\u0161t\u011bna rozd\u00edln\u00e1 metylace.<\/p>\n\n\n\n

Krom\u011b zji\u0161t\u011bn\u00ed zam\u011b\u0159en\u00fdch na TAPBP zjistili, \u017ee UV mutace jsou spojeny s \u0159adou epigenetick\u00fdch zm\u011bn, kter\u00e9 ovliv\u0148uj\u00ed metylom ko\u017en\u00edho melanomu. V\u00fdsledky nazna\u010duj\u00ed, \u017ee ko\u017en\u00ed melanomy, a\u0165 u\u017e s UV mutac\u00ed, nebo bez n\u00ed, bude mo\u017en\u00e1 nutn\u00e9 klasifikovat odd\u011blen\u011b, i kdy\u017e se p\u0159edpokl\u00e1d\u00e1, \u017ee maj\u00ed stejn\u00fd patologick\u00fd\/ bun\u011b\u010dn\u00fd p\u016fvod. Je to proto, \u017ee epigenomick\u00e1 krajina, ze kter\u00e9 jsou odvozeny, m\u016f\u017ee obsahovat jak markery expozice, tak bun\u011b\u010dn\u00e9 linie. <\/p>\n\n\n\n

V t\u00e9to studii bylo na vzorky ko\u017en\u00edho a akr\u00e1ln\u00edho melanomu pou\u017eito n\u011bkolik v\u00fdkonn\u00fdch technologi\u00ed, v\u010detn\u011b WGS, WES, sekvenov\u00e1n\u00ed RNA a profilov\u00e1n\u00ed cel\u00e9ho metylomu DNA, spolu s nejmodern\u011bj\u0161\u00edmi bioinformatick\u00fdmi n\u00e1stroji. V\u00fdzkumn\u00edci vyu\u017eili ve\u0159ejn\u011b dostupn\u00e1 data a doplnili je o nov\u00e9 soubory dat, kter\u00e9 zahrnovaly v\u011bt\u0161\u00ed velikost vzork\u016f, \u0161ir\u0161\u00ed genomick\u00e9 pokryt\u00ed, komplexn\u00ed fenotypov\u00e9 hodnocen\u00ed, dob\u0159e zachoval\u00e9 vzorky zmra\u017een\u00e9 tk\u00e1n\u011b a hodnocen\u00ed melanom\u016f krom\u011b ko\u017en\u00edch i jin\u00fdch etnik ne\u017e Evropan\u016f. <\/p>\n\n\n\n

V\u00fdsledkem t\u00e9to pr\u00e1ce jsou tyto v\u00fdsledky<\/h2>\n\n\n\n

(1) Objev biomarker\u016f, kter\u00e9 lze pou\u017e\u00edt ke stratifikaci rizika rakoviny;<\/p>\n\n\n\n

(2) Zlep\u0161en\u00ed klasifikace typ\u016f melanomu v r\u00e1mci jednotliv\u00fdch typ\u016f a mezi nimi; <\/p>\n\n\n\n

(3) Identifikovat molekul\u00e1rn\u00ed faktory, kter\u00e9 mohou b\u00fdt zodpov\u011bdn\u00e9 za melanomagenezi a na kter\u00e9 lze c\u00edlit p\u0159i terapii; <\/p>\n\n\n\n

(4) Zvy\u0161ov\u00e1n\u00ed znalost\u00ed o patobiologii melanomu s c\u00edlem sn\u00ed\u017eit rozd\u00edly v populaci.<\/p>\n\n\n\n

Tato studie poskytuje pl\u00e1n pro podobn\u00fd v\u00fdzkum gen\u016f a prost\u0159ed\u00ed u jin\u00fdch typ\u016f melanomu a zahrnuje jak b\u011b\u017en\u00e9, tak m\u00e9n\u011b \u010dast\u00e9 melanomy.<\/p>\n\n\n\n

Efektivn\u011bj\u0161\u00ed zp\u016fsob sd\u011blov\u00e1n\u00ed p\u0159esn\u00fdch v\u011bdeck\u00fdch informac\u00ed<\/h2>\n\n\n\n

Tento v\u00fdzkumn\u00fd \u010dl\u00e1nek je velmi zaj\u00edmav\u00fd a snadno pochopiteln\u00fd, p\u0159edev\u0161\u00edm d\u00edky kr\u00e1sn\u00fdm grafick\u00fdm ilustrac\u00edm. Grafy byly vytvo\u0159eny pomoc\u00ed Mind the Graph<\/a> n\u00e1stroj. Grafick\u00e1 ilustrace m\u016f\u017ee b\u00fdt pro \u010dten\u00e1\u0159e p\u0159\u00ednosn\u00e1 r\u016fzn\u00fdmi zp\u016fsoby. M\u016f\u017eete si zkusit zv\u00fd\u0161it \u00farove\u0148 sv\u00e9ho v\u00fdzkumu t\u00edm, \u017ee se zdarma zaregistrujete na Mind the Graph a vyzkou\u0161\u00edte si prvn\u00ed v\u011bdeck\u00fd obr\u00e1zek.

Nezapome\u0148te se pod\u00edvat na n\u00e1\u0161 \u010dl\u00e1nek \"V\u011bdeck\u00e1 ilustrace: Kl\u00ed\u010d ke sv\u011btu vizu\u00e1ln\u00ed v\u011bdy<\/a>“. <\/p>\n\n\n\n

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Vytv\u00e1\u0159ejte efektivn\u00ed v\u011bdeck\u00e9 postavy b\u011bhem n\u011bkolika minut<\/a><\/div>\n<\/div>\n\n\n\n
<\/div>","protected":false},"excerpt":{"rendered":"

Tento \u010dl\u00e1nek se bude zab\u00fdvat prognostick\u00fdmi faktory rakoviny souvisej\u00edc\u00edmi s patobiologi\u00ed a expozic\u00ed ultrafialov\u00e9mu z\u00e1\u0159en\u00ed spolu s post\u0159ehy autora.<\/p>","protected":false},"author":27,"featured_media":27204,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[956],"tags":[937,96,554,775],"yoast_head":"\nResearch Review: Cutaneous and Acral Melanoma<\/title>\n<meta name=\"description\" content=\"This article will discuss the prognostic cancer driver related to pathobiology and ultraviolet exposure along with the author's insights.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/mindthegraph.com\/blog\/cs\/kozni-a-akralni-melanom\/\" \/>\n<meta property=\"og:locale\" content=\"cs_CZ\" \/>\n<meta property=\"og:type\" content=\"article\" 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As a science enthusiast, she is keen in learning more about the scientific world and wants to play a part in making a difference.","sameAs":["http:\/\/linkedin.com\/in\/aayushizaveri"],"url":"https:\/\/mindthegraph.com\/blog\/cs\/author\/aayuyshi\/"}]}},"_links":{"self":[{"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/posts\/19837"}],"collection":[{"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/users\/27"}],"replies":[{"embeddable":true,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/comments?post=19837"}],"version-history":[{"count":10,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/posts\/19837\/revisions"}],"predecessor-version":[{"id":27210,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/posts\/19837\/revisions\/27210"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/media\/27204"}],"wp:attachment":[{"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/media?parent=19837"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/categories?post=19837"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mindthegraph.com\/blog\/cs\/wp-json\/wp\/v2\/tags?post=19837"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}