Un-Fair Skin: racial disparities in acral melanoma research.
Ontology highlight
ABSTRACT:
SUBMITTER: Alicea GM
PROVIDER: S-EPMC9844516 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
Un-Fair Skin: racial disparities in acral melanoma research.
Alicea Gretchen M GM Rebecca Vito W VW
Nature reviews. Cancer 20220301 3
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Project description: Not available
| S-EPMC9925091 | biostudies-literature
Project description:Adult and childhood obesity and related adverse outcomes are most common among racial/ethnic minorities and socio-economically disadvantaged populations in the United States . Research approaches to obesity developed in mainstream populations and deploying new information technologies may exacerbate existing disparities in obesity. Current obesity management and prevention research priorities will not maximally impact this critical problem unless investigators explicitly focus on discovering innovative strategies for preventing and managing obesity in the disadvantaged populations that are most affected. On the basis of our research experience, four key research approaches are needed: (1) elucidating the underlying social forces that lead to disparities; (2) directly involving community members in the development of research questions and research methods; (3) developing flexible strategies that allow tailoring to multiple disadvantaged populations; and (4) building culturally and socio-economically tailored strategies specifically for populations most affected by obesity. Our experience with a community-based longitudinal cohort study and two health center-based clinical trials illustrate these principles as a contrast to traditional research priorities that can inadvertently worsen existing social inequities. If obesity research does not directly address healthcare and health-outcome disparities, it will contribute to their perpetuation.
| S-EPMC3647479 | biostudies-other
Project description:Acral lentiginous melanoma is a histological subtype of cutaneous melanoma that occurs in the glabrous skin of the palms, soles and the nail unit. Although in some countries, particularly in Latin America, Africa and Asia, it represents the most frequently diagnosed subtype of the disease, it only represents a small proportion of melanoma cases in European-descent populations, which is partially why it has not been studied to the same extent as other forms of melanoma. As a result, its unique genomic drivers remain comparatively poorly explored, as well as its causes, with current evidence supporting a UV-independent path to tumorigenesis. In this review, we discuss current knowledge of the aetiology and diagnostic criteria of acral lentiginous melanoma, as well as its epidemiological and histopathological characteristics. We also describe what is known about the genomic landscape of this disease and review the available biological models to explore potential therapeutic targets.
| S-EPMC7818404 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-14 | GSE162682 | GEO
Project description:Objective:This study evaluates whether different dimensions of physiological dysregulation, modeled individually rather than additively mediate racial/ethnic disparities in self-reported health. Methods:Using data from the National Health and Nutrition Examination Survey (2005-2010) and the Karlson, Hold, and Breen (KHB) mediation model, this paper explores what operationalization of biomarker data most strongly mediate racial/ethnic disparities in poor/fair self-rated health (SRH) among adults in the United States, net of demographic, socioeconomic, behavioral, and medication controls. Results:Non-Hispanic blacks and Hispanics had significantly higher odds of reporting poor/fair self-rated health in comparison to non-Hispanic whites. Operationalizations of allostatic load that disaggregate three major dimensions of physiological dysregulation mediate racial/ethnic disparities strongly between non-Hispanic blacks and non-Hispanic whites, but not between Hispanics and non-Hispanic whites. Disaggregating these dimensions explains racial/ethnic disparities in poor/fair SRH better than the continuous score. Analyses on sex-specific disparities indicate differences in how individual dimensions of allostatic load contribute to racial/ethnic disparities in poor/fair SRH differently. All individual dimensions are strong determinants of poor/fair SRH for males. In contrast, for females, the only dimension that is significantly associated with poor/fair SRH is inflammation. For the analytic sample, additive biomarker scores fit the data as well or better than other approaches, suggesting that this approach is most appropriate for explaining individual differences. However, in sex-specific analyses, the interactive approach models fit the data best for men and women. Conclusions:Future researchers seeking to explain racial/ethnic disparities in full or sex-stratified samples should consider disaggregating allostatic load by dimension.
| S-EPMC5769108 | biostudies-literature
Project description:Acral melanoma is an aggressive type of melanoma with unknown origins, arising on the sole, palm, or nail apparatus. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. Our study examined exome sequencing data from 139 tissue samples, spanning different progression stages, collected from 37 patients. We found that 78.4% of the melanomas displayed one or more clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22. These genomic "hailstorms" were typically shared across all progression stages within individual patients. Genetic alterations known to activate TERT also arose early. By contrast, mutations in the MAP-kinase pathway appeared later during progression, often leading to different tumor areas harboring non-overlapping driver mutations. We conclude that the evolutionary trajectories of acral melanomas substantially diverge from those of melanomas on sun-exposed skin, where MAP-kinase pathway activation initiates the neoplastic cascade followed by immortalization later. The punctuated formation of hailstorms, paired with early TERT activation, suggests a unique mutational mechanism underlying the origins of acral melanoma. Our findings highlight an essential role for telomerase, likely in re-stabilizing tumor genomes after hailstorms have initiated the tumors. The marked genetic heterogeneity, in particular of MAP-kinase pathway drivers, may partly explain the limited success of targeted and other therapies in treating this melanoma subtype.
| S-EPMC10614839 | biostudies-literature
Project description:BackgroundAcral melanoma is a rare type of melanoma that affects world populations irrespective of skin color and has worse survival than other cutaneous melanomas. It has relatively few single nucleotide mutations without the UV signature of cutaneous melanomas, but instead has a genetic landscape characterized by structural rearrangements and amplifications. BRAF mutations are less common than in other cutaneous melanomas, and knowledge about alternative therapeutic targets is incomplete.MethodsTo identify alternative therapeutic targets, we performed targeted deep-sequencing on 122 acral melanomas. We confirmed the loss of the tumor suppressors p16 and NF1 by immunohistochemistry in select cases.ResultsIn addition to BRAF (21.3%), NRAS (27.9%), and KIT (11.5%) mutations, we identified a broad array of MAPK pathway activating alterations, including fusions of BRAF (2.5%), NTRK3 (2.5%), ALK (0.8%), and PRKCA (0.8%), which can be targeted by available inhibitors. Inactivation of NF1 occurred in 18 cases (14.8%). Inactivation of the NF1 cooperating factor SPRED1 occurred in eight cases (6.6%) as an alternative mechanism of disrupting the negative regulation of RAS. Amplifications recurrently affected narrow loci containing PAK1 and GAB2 (n = 27, 22.1%), CDK4 (n = 27, 22.1%), CCND1 (n = 24, 19.7%), EP300 (n = 20, 16.4%), YAP1 (n = 15, 12.3%), MDM2 (n = 13, 10.7%), and TERT (n = 13, 10.7%) providing additional and possibly complementary therapeutic targets. Acral melanomas with BRAFV600E mutations harbored fewer genomic amplifications and were more common in patients with European ancestry.ConclusionOur findings support a new, molecularly based subclassification of acral melanoma with potential therapeutic implications: BRAFV600E mutant acral melanomas with characteristics similar to nonacral melanomas that could benefit from BRAF inhibitor therapy, and non-BRAFV600E mutant acral melanomas. Acral melanomas without BRAFV600E mutations harbor a broad array of therapeutically relevant alterations. Expanded molecular profiling would increase the detection of potentially targetable alterations for this subtype of acral melanoma.
| S-EPMC6792090 | biostudies-literature
Project description:Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel immunotherapeutic regimes aiming to recover the antitumor function of immune cells. We studied a Mexican cohort of melanoma patients from the Mexican Institute of Social Security (IMSS) (n = 38) and found an overrepresentation of AM (73.9%). We developed a multiparametric immunofluorescence technique coupled with a machine learning image analysis to evaluate the presence of conventional type 1 dendritic cells (cDC1) and CD8 T cells in the stroma of melanoma, two of the most relevant immune cell types for antitumor responses. We observed that both cell types infiltrate AM at similar and even higher levels than other cutaneous melanomas. Both melanoma types harbored programmed cell death protein 1 (PD-1+) CD8 T cells and PD-1 ligand (PD-L1+) cDC1s. Despite this, CD8 T cells appeared to preserve their effector function and expanding capacity as they expressed interferon-γ (IFN-γ) and KI-67. The density of cDC1s and CD8 T cells significantly decreased in advanced stage III and IV melanomas, supporting these cells' capacity to control tumor progression. These data also argue that AM could respond to anti-PD-1-PD-L1 immunotherapy.
| S-EPMC10003718 | biostudies-literature
Project description:Numerous epidemiologic studies have documented environmental health disparities according to race/ethnicity (R/E) to inform targeted interventions aimed at reducing these disparities. Yet, the use of R/E under the potential outcomes framework implies numerous underlying assumptions for epidemiologic studies that are often not carefully considered in environmental health research. In this commentary, we describe the current state of thinking about the interpretation of R/E variables in etiologic studies. We then discuss how such variables are commonly used in environmental epidemiology. We observed three main uses for R/E: i) as a confounder, ii) as an effect measure modifier and iii) as the main exposure of interest either through descriptive analysis or under a causal framework. We identified some common methodological concerns in each case and provided some practical solutions. The use of R/E in observational studies requires particular cautions in terms of formal interpretation and this commentary aims at providing a practical resource for future studies assessing racial/ethnic health disparities in environmental research.
| S-EPMC7802337 | biostudies-literature