Deconvoluted methylation profiles discriminate between closely related melanocytic nevi
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE268769 | GEO | 2024/06/17
REPOSITORIES: GEO
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In this step, enrichment analysis underlined the alteration of biological processes linked to apoptosis. Upregulation of genes involved into DNA double-strand breaks repair and downregulation of cellular adhesion genes were observed in MTS respect to VGPM. Futhermore, the gene expression profiles of 11 dysplastic nevi (DN) were compared to all the others. Some genes controlling proliferation were found more expressed than in CMN. Overall, DN displayed an heterogeneous behaviour, with relevant oncogenes, such as MYC and BCL6, less expressed than in RGPM, and a modulation pattern similar to VGPM for a subset of gene families, such as mismatch repair. This suggests that DN is not an intermediate step within melanoma progression, but a separate entity with an independent risk of progression to melanoma Experiment Overall Design: In order to identify genes implicated during the course of melanoma development and progression, a total of 57 excisional biopsies from common melanocytic nevi (n = 18), dysplastic nevi (n = 11), primary radial growth phase malignant melanomas (n = 8), primary vertical growth phase malignant melanomas (n = 15) and melanoma metastases (n = 5) were analyzed. Total RNA was isolated by using RNeasy Mini Kit (Qiagen, Dusseldorf, Germany). TotRNA quality was checked by means of RNA 6000 pico chip assays (Agilent Technologies, Palo Alto, CA) run on the Agilent 2100 bioanalyzer. RNA isolated from each fresh tissue and from the human universal reference (BD™ Human Universal Reference Total RNA, Clontech, Palo Alto, CA) was amplified by means of the Amino Allyl MessageAmp II aRNA Kit (Ambion) to obtain amino allyl antisense RNA (aaRNA) following the method developed by Eberwine and coworkers. Two rounds of amplification were performed to obtain the necessary quantity of aaRNA for labeling. Briefly: mRNA was reverse transcribed in cDNA single strand; after the second strand synthesis (in the second round of amplification), cDNA was in vitro transcribed in aaRNA including amino allyl modified nucleotides (aaUTP). Both dsDNA and aaRNA underwent a purification step using columns provided with the kit. Labeling was performed using NHS ester Cy3 or Cy5 dyes (Amersham Biosciences, Buckinghamshire UK) able to react with the modified RNA. mRNA quality was checked by means of RNA 6000 nano chip assays (Agilent Technologies). 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