{"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\/nb\/kutane-og-akrale-melanomer\/","title":{"rendered":"Forskningsgjennomgang: Kutant og akralt melanom"},"content":{"rendered":"

I flere ti\u00e5r har det blitt rapportert om en \u00f8kning i melanomforekomsten i enkelte befolkningsgrupper verden over. En svulst i melanocytter i hud, slimhinner eller uvea kalles melanom. Til tross for at melanom utgj\u00f8r 5% av alle kutane maligniteter, er det ansvarlig for mer enn 75% av alle d\u00f8dsfall som skyldes hudkreft.\u00a0<\/p>\n\n\n\n

Selv om den positive sammenhengen mellom UV-eksponering og utvikling av f\u00f8flekkreft er velkjent, er de underliggende epigenetiske mekanismene i humant f\u00f8flekkreftvev i stor grad uutforsket. Denne artikkelen vil diskutere den prognostiske kreftdriveren knyttet til patobiologi og ultrafiolett eksponering, sammen med forfatterens innsikt i det nevnte emnet. <\/p>\n\n\n\n

Form\u00e5let med studien<\/h2>\n\n\n\n

Ved hjelp av to uavhengige kohorter av hudmelanompasienter skal de oppdage og validere genomomfattende metyleringsendringer knyttet til UV-mutasjoner. Et hovedm\u00e5l er \u00e5 unders\u00f8ke det diagnostiske potensialet til DNA-metylomer i forhold til transkriptomer og integrerte metylom-transkriptomer for \u00e5 skille mellom UV-muterte og ikke-UV-muterte kutane melanomer. <\/p>\n\n\n\n

Using an integrative OMIC approach, the small nucleotide variants (SNVs) and copy number variants (CNVs) of prioritized differentially methylated genes are assessed for cancer driver potential. This research is further supported by another that examines whether DNA methylomes can distinguish pathological and UV-related differences between prominent melanoma variants that are associated with exposure to UV light (cutaneous melanoma) and those that are not (acral melanoma). The diagram in the paper shows what the study’s goal and process are. The graphical representation was created using Mind the Graph<\/a><\/strong>.<\/p>\n\n\n\n

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Gjennomgang av studien i detalj<\/h2>\n\n\n\n

I kliniske biopr\u00f8ver har UV-str\u00e5ling (UV) blitt knyttet til kutant melanom, men de epigenetiske mekanismene som ligger til grunn for disse mekanismene, er enn\u00e5 ikke klarlagt. En multietnisk kohort med 112 kutane melanomceller ble inkludert i denne studien for klinisk, epigenom- (DNA-metylom), genom- og transkriptomprofilering. I denne studien identifiserer de UV-induserte endringer i immunologiske og regulatoriske veier som kan v\u00e6re kreftfremkallende p\u00e5 tvers av multi-OMIC.<\/p>\n\n\n\n

I tillegg til \u00e5 v\u00e6re det mest kritisk involverte genet, er TAPBP (Tap binding protein gene) kritisk involvert i immunfunksjonen, med flere UV-endrede metyleringssteder som er validert ved m\u00e5lrettet sekvensering, noe som gir klinisk anvendbare muligheter. MHC-I interagerer med transport\u00f8ren assosiert med antigenprosessering gjennom TAPBP, et medlem av immunglobulinsuperfamilien. En rekke kreftformer har vist nedregulering av TAPBP-proteinet (tapasin), som gjenopprettes etter cytokineksponering.\u00a0<\/p>\n\n\n\n

Dette tyder p\u00e5 at mangelfullt TAPBP-uttrykk kan skyldes dysregulering snarere enn strukturelle endringer. Forskerne fant at DNA-metyleringsniv\u00e5ene av TAPBP er signifikant omvendt relatert til transkripsjon, og at sistnevnte endres som f\u00f8lge av UV-eksponering snarere enn melanomets patologiske identitet. Verken kutane eller akrale melanomer som ikke er UV-muterte, ble funnet \u00e5 v\u00e6re differensielt metylerte.<\/p>\n\n\n\n

I tillegg til funnene knyttet til TAPBP, fant de at UV-mutasjoner er assosiert med en rekke epigenetiske endringer som p\u00e5virker metylomet i kutant melanom. Resultatene tyder p\u00e5 at kutane melanomer, enten de er UV-muterte eller ikke-UV-muterte, m\u00e5 klassifiseres separat, selv om de antas \u00e5 ha samme patologiske\/cellul\u00e6re opprinnelse. Dette skyldes at det epigenomiske landskapet de er avledet fra, kan inneholde b\u00e5de mark\u00f8rer for eksponering og cellelinje. <\/p>\n\n\n\n

I denne studien ble det brukt flere kraftfulle teknologier p\u00e5 hud- og akralmelanompr\u00f8ver, inkludert WGS, WES, RNA-sekvensering og DNA-metylomomfattende profilering, sammen med avanserte bioinformatiske verkt\u00f8y. Forskerne brukte offentlig tilgjengelige data og supplerte dem med nye datasett, som inkluderte st\u00f8rre pr\u00f8vest\u00f8rrelser, bredere genomisk dekning, omfattende fenotypiske vurderinger, godt bevarte frosne vevspr\u00f8ver og evaluering av melanomer i tillegg til kutane og andre etnisiteter enn europeere. <\/p>\n\n\n\n

Dette arbeidet resulterte i f\u00f8lgende resultater<\/h2>\n\n\n\n

(1) Oppdage biomark\u00f8rer som kan brukes til \u00e5 stratifisere kreftrisiko;<\/p>\n\n\n\n

(2) Forbedret klassifisering av melanomtyper innenfor og mellom dem; <\/p>\n\n\n\n

(3) Identifisere molekyl\u00e6re drivere som kan v\u00e6re ansvarlige for melanomagenese, og som kan brukes som m\u00e5l for behandling; <\/p>\n\n\n\n

(4) \u00d8ke kunnskapen om melanompatobiologi for \u00e5 redusere forskjellene i befolkningen.<\/p>\n\n\n\n

Denne studien gir et veikart for lignende gen-milj\u00f8-unders\u00f8kelser i andre typer melanom og dekker b\u00e5de vanlige og mindre vanlige melanomer.<\/p>\n\n\n\n

En mer effektiv m\u00e5te \u00e5 kommunisere n\u00f8yaktig vitenskapelig informasjon p\u00e5<\/h2>\n\n\n\n

Denne forskningsrapporten er sv\u00e6rt interessant og lett \u00e5 forst\u00e5, hovedsakelig p\u00e5 grunn av de flotte grafiske illustrasjonene. Grafene ble laget ved hjelp av Mind the Graph<\/a> verkt\u00f8y. En grafisk illustrasjon kan v\u00e6re til nytte for leseren p\u00e5 flere m\u00e5ter. Du kan pr\u00f8ve \u00e5 f\u00e5 fart p\u00e5 forskningen din ved \u00e5 registrere deg gratis p\u00e5 Mind the Graph og pr\u00f8ve din f\u00f8rste vitenskapelige figur.

Ikke glem \u00e5 sjekke ut artikkelen v\u00e5r \"Vitenskapelig illustrasjon: N\u00f8kkelen til en verden av visuell vitenskap<\/a>“. <\/p>\n\n\n\n

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Lag effektive vitenskapelige figurer p\u00e5 f\u00e5 minutter<\/a><\/div>\n<\/div>\n\n\n\n
<\/div>","protected":false},"excerpt":{"rendered":"

Denne artikkelen diskuterer de prognostiske kreftdriverne knyttet til patobiologi og ultrafiolett eksponering sammen med forfatterens innsikt.<\/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\/nb\/kutane-og-akrale-melanomer\/\" \/>\n<meta property=\"og:locale\" content=\"nb_NO\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Paper Review: Cutaneous and 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