Gene expression profiles of benign nevi and cutaneous melanomas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: Erkki Holtta
PROVIDER: E-MTAB-1862 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:DNA methylation, an epigenetic alteration typically occurring early in cancer development, could aid in the molecular diagnosis of melanoma. We determined technical feasibility for high-throughput DNA-methylation array-based profiling using formalin-fixed paraffin-embedded tissues for selection of candidate DNA-methylation differences between melanomas and nevi. Promoter methylation was evaluated in 27 common benign nevi and 22 primary invasive melanomas using a 1505 CpG site microarray. Unsupervised hierarchical clustering distinguished melanomas from nevi; 26 CpG sites in 22 genes were identified with significantly different methylation levels between melanomas and nevi after adjustment for age, sex, and multiple comparisons and with β-value differences of ≥ 0.2. Prediction analysis for microarrays identified 12 CpG loci that were highly predictive of melanoma, with area under the receiver operating characteristic curves of > 0.95. Of our panel of 22 genes, 14 were statistically significant in an independent sample set of 29 nevi (including dysplastic nevi) and 25 primary invasive melanomas after adjustment for age, sex, and multiple comparisons. This first report of a DNA-methylation signature discriminating melanomas from nevi indicates that DNA methylation appears promising as an additional tool for enhancing melanoma diagnosis.
| S-EPMC3073305 | biostudies-literature
Project description:In the present study, we employed the ddPCR and IHC techniques to assess the prevalence and roles of RAS and RAF mutations in a small batch of melanoma (n = 22), benign moles (n = 15), and normal skin samples (n = 15). Mutational screening revealed the coexistence of BRAF and NRAS mutations in melanomas and nevi and the occurrence of NRAS G12/G13 variants in healthy skin. All investigated nevi had driver mutations in the BRAF or NRAS genes and elevated p16 protein expression, indicating cell cycle arrest despite an increased mutational burden. BRAF V600 mutations were identified in 54% of melanomas, and NRAS G12/G13 mutations in 50%. The BRAF mutations were associated with the Breslow index (BI) (p = 0.029) and TIL infiltration (p = 0.027), whereas the NRAS mutations correlated with the BI (p = 0.01) and the mitotic index (p = 0.04). Here, we demonstrate that the "young" ddPCR technology is as effective as a CE-IVD marked real-time PCR method for detecting BRAF V600 hotspot mutations in tumor biopsies and recommend it for extended use in clinical settings. Moreover, ddPCR was able to detect low-frequency hotspot mutations, such as NRAS G12/G13, in our tissue specimens, which makes it a promising tool for investigating the mutational landscape of sun-damaged skin, benign nevi, and melanomas in more extensive clinical studies.
| S-EPMC10889428 | biostudies-literature
Project description:We performed exome sequencing of 77 melanocytic specimens composed of Spitz nevi (n=29), Spitzoid melanomas (n=27), and benign melanocytic nevi (n=21), and compared the results with published melanoma sequencing data. Our study highlights the prominent similarity between Spitzoid and conventional melanomas with similar copy number changes and high and equal numbers of ultraviolet-induced coding mutations affecting similar driver genes. Mutations in MEN1, PRKAR1A, and DNMT3A in Spitzoid melanomas may indicate involvement of the protein kinase A pathway, or a role of DNA methylation in the disease. Other than activating HRAS variants, there were few additional mutations in Spitz nevi, and few copy number changes other than 11p amplification and chromosome 9 deletions. Similarly, there were no large-scale copy number alterations and few somatic alterations other than activating BRAF or NRAS mutations in conventional nevi. A presumed melanoma driver mutation (IDH1Arg132Cys) was revealed in one of the benign nevi. In conclusion, our exome data show significantly lower somatic mutation burden in both Spitz and conventional nevi compared with their malignant counterparts, and high genetic similarity between Spitzoid and conventional melanoma.
| S-EPMC5413430 | biostudies-literature
Project description:The use of microRNAs as biomarkers has been proposed for many diseases, including the diagnosis of melanoma. Although hundreds of microRNAs have been identified as differentially expressed in melanomas as compared to benign melanocytic lesions, a limited consensus has been achieved across studies, constraining the effective use of these potentially useful markers. In this study, we applied a machine learning-based pipeline to a dataset consisting of genetic features, clinical features, and next-generation microRNA sequencing from micro-dissected formalin-fixed paraffin embedded melanomas and their adjacent benign precursor nevi. We identified patient age and tumor cellularity as variables that frequently confound the measured expression of potentially diagnostic microRNAs. By employing the ratios of microRNAs that were either enriched or depleted in melanoma compared to the nevi as a normalization strategy, we developed a model that classified all the available published cohorts with an area under the receiver operating characteristic curve of 0.98. External validation on an independent cohort classified lesions with 81% sensitivity and 88% specificity and was uninfluenced by the tumor content of the sample or patient age.
| S-EPMC6926155 | biostudies-literature
Project description:Reflectance confocal microscopy (RCM) together with dermoscopy enables improved differentiation of melanomas from most nevi. The resulting high sensitivity for detecting melanoma with RCM is complemented by a concomitant increased specificity, which results in the reduction of unnecessary biopsies of nevi. Although RCM can achieve high diagnostic accuracy for early melanoma detection, false-negative and false-positive cases of melanoma are occasionally encountered. This article reviews the essential clues and pitfalls for the diagnosis of melanoma via RCM and highlights the importance of evaluating RCM findings in light of the clinical scenario and dermoscopic features.
| S-EPMC5572798 | biostudies-other
Project description:Background/Objectives: Genetics and epigenetics play an important role in the pathogenesis of cutaneous melanoma. The majority of cases harbor mutations in genes associated with the MAPK signaling pathway, i.e., BRAF, NRAS, or NF1. The remaining neoplasms, often located on acral sites, are condensed as the triple-wildtype subtype and are characterized by other molecular drivers. This study aimed to elucidate genetic and epigenetic differences within cutaneous melanoma and to compare it with melanocytic nevi. Methods: DNA was extracted from archived tissue samples of cutaneous melanoma (n = 19), melanocytic nevi (n = 11), and skin controls (n = 11) and subsequently analyzed by massive parallel (next generation) gene panel sequencing and genome-wide DNA methylation array analysis. The sample size was increased by including repository data from an external study. Results: There were major differences in the genomic landscape of MAPK-altered and triple-wildtype cutaneous melanoma, the latter presenting with a lower number of mutations, a different pattern of copy number variants, and a low frequency of TERT promoter mutations. Dimensional reduction of DNA methylation array analysis clearly separated cutaneous melanoma from melanocytic nevi but revealed no major differences between classical cutaneous melanoma and the triple-wildtype cases. However, it identified a possible biological subgroup characterized by intermediately methylated CpGs. Conclusions: Dimensional reduction of methylation array data is a useful tool for the analysis of melanocytic tumors to differentiate between malignant and benign lesions and may be able to identify biologically distinct subtypes of cutaneous melanoma.
| S-EPMC11899029 | biostudies-literature
Project description:PurposeTo evaluate the outcomes of argon laser photoablation of benign conjunctival pigmented nevi with different clinical presentations.Patients and methodsThis interventional case series was conducted between July 2014 and January 2015. Patients presenting with benign conjunctival nevi were included. Data were collected on the clinical features at presentation, argon laser photoablation, and follow-up at 8 and 24 weeks. Postoperative photography allowed recording of the success of each case and the overall success rate. Complete removal of conjunctival pigments was considered an absolute success. Partial pigmentation requiring repeat laser treatment was considered a qualified success.ResultsThere were 14 eyes (four right eyes and ten left eyes) with benign pigmented conjunctival nevi. There were three males and eight females in the study sample. The median age was 36 (25% percentile: 26 years). Three patients had bilateral lesions. The nevi were located temporally in nine eyes, nasally in three eyes, and on the inferior bulbar conjunctiva in two eyes. The mean horizontal and vertical diameters of nevi were 5 ± 2 mm and 4 ± 2.7 mm, respectively. The mean follow-up period was 5 months. Following laser treatment, no eyes had subconjunctival hemorrhage, infection, scarring, neovascularization, recurrence, or corneal damage. The absolute success rate of laser ablation was 79%. Three eyes with elevated nevi had one to three sessions of laser ablation resulting in a qualified success rate of 100%.ConclusionsArgon laser ablation was a safe and effective treatment for the treatment of selective benign pigmented conjunctival nevi in Arab patients.
| S-EPMC4968145 | biostudies-literature
Project description:Human CD4+ T cells mediate spontaneous rejection of acquired benign melanocytic nevi, in the majority of cases, through a break in peripheral tolerance. For the remaining cases, nevi remain stable and do not progress to malignancy. In this experiment, we compared gene expression of post-transplant rejected nevi to stable nevi in order to better characterize their transcriptional profiles.
2021-07-08 | GSE153399 | GEO
Project description:We examined nevi and melanomas in 10 xeroderma pigmentosum (XP) patients with defective DNA repair. The lesions had a lentiginous appearance with markedly increased numbers of melanocytes. Using laser capture microdissection, we performed DNA sequencing of 18 benign and atypical nevi and 75 melanomas (melanoma in situ and invasive melanomas). The nevi had a similar high frequency of PTEN mutations as melanomas [61% (11/18) versus 53% (39/73)]. Both had a very high proportion of UV-type mutations (occurring at adjacent pyrimidines) [91% (10/11) versus 92% (36/39)]. In contrast to melanomas in the general population, the frequency of BRAF mutations (11%, 7/61), NRAS mutations (21%, 13/62), and KIT mutations (21%, 6/28) in XP melanomas was lower than for PTEN. Phospho-S6 immunostaining indicated activation of the mTOR pathway in the atypical nevi and melanomas. Thus, the clinical and histological appearances and the molecular pathology of these UV-related XP nevi and melanomas were different from nevi and melanomas in the general population.
| S-EPMC6309892 | biostudies-literature
Project description:AimTo examine the association of cutaneous nevi with Type 2 diabetes risk.MethodsWe prospectivly examined the associations between nevus count and risk of Type 2 diabetes among 26 240 men (1988-2010) from the Health Professionals Follow-up Study and 67 050 women (1986-2010) from the Nurses' Health Study. Information on the numbers of cutaneous nevi on arms at baseline and incident cases of Type 2 diabetes was collected using validated questionnaires.ResultsDuring 1 879 287 person-years of follow-up, we documented 9040 incident cases of Type 2 diabetes. After adjustment for age, BMI and other diabetes risk factors, greater number of nevi was associated with higher risk of Type 2 diabetes. Multivariable-adjusted hazard ratios for <1, 1-5, 6-14 and ≥15 nevi were 1.00 (reference), 1.02 (95% CI 0.93, 1.13), 1.08 (95% CI 0.88, 1.34) and 1.57 (95% CI 1.15, 2.15), respectively, for men (P for linear trend = 0.01), and 1.00 (reference), 1.07 (95% CI 1.02, 1.13), 0.98 (95% CI 0.87, 1.10), and 1.25 (1.01, 1.54), respectively, for women (P for linear trend = 0.05). This positive association remained consistent across subgroups stratified by age, BMI, multivitamin use, smoking status, alcohol, physical activity, history of hypercholesterolaemia, family history of diabetes, history of hypertension and menopausal status (in women).ConclusionsCutaneous nevus count may represent a novel marker for development of Type 2 diabetes, suggesting a possible unique melanocytic nevus-related mechanism in the pathogenesis of Type 2 diabetes. Further studies are warranted to confirm the findings and to investigate the underlying mechanisms.
| S-EPMC5459671 | biostudies-literature