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Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma | Cancer Research
Cutaneous malignant melanoma (melanoma) is characterized by a high mutational load, extensive intertumoral and intratumoral genetic heterogeneity, and complex tumor microenvironment (TME) interactions. Further insights into the mechanisms underlying melanoma are crucial for understanding tumor progression and responses to treatment. Here we adapted the technology of spatial transcriptomics (ST) to melanoma lymph node biopsies and successfully sequenced the transcriptomes of over 2,200 tissue domains. Deconvolution combined with traditional approaches for dimensional reduction of transcriptome-wide data enabled us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Our unsupervised analysis revealed a complex spatial intratumoral composition of melanoma metastases that was not evident through morphologic annotation. Each biopsy showed distinct gene expression profiles and included examples of the coexistence of multiple melanoma signatures within a single tumor region as well as shared profiles for lymphoid tissue characterized according to their spatial location and gene expression profiles. The lymphoid area in close proximity to the tumor region displayed a specific expression pattern, which may reflect the TME, a key component to fully understanding tumor progression. In conclusion, using the ST technology to generate gene expression profiles reveals a detailed landscape of melanoma metastases. This should inspire researchers to integrate spatial information into analyses aiming to identify the factors underlying tumor progression and therapy outcome.

Significance: Applying ST technology to gene expression profiling in melanoma lymph node metastases reveals a complex transcriptional landscape in a spatial context, which is essential for understanding the multiple components of tumor progression and therapy outcome.
spatial_transcriptomics  melanoma 
march 2019 by Segalllab
Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution: Cancer Cell
This study further delineates the sequential order in which signaling pathways become disrupted as benign and intermediate precursors evolve to melanoma in situ, invasive melanoma, and metastases. Activation of the MAPK pathway induces a benign nevus, constrained by replicative senescence, G1/S arrest, and chromatin organization. These barriers are incrementally overrun during melanoma formation, and melanomas continue to accumulate genetic alterations that ramp-up MAPK pathway signaling output and perturb the p53 and PI3K pathways. No mutations were specifically associated with metastatic dissemination to regional sites. Overall, we identify crucial steps in the development of melanoma, which can be subject to future treatments and can guide biomarker strategies to improve diagnosis and staging.
gene_expression  progression  tumorigenesis  melanoma 
march 2019 by Segalllab
How do metastatic tumor cells grow in lymph nodes? Tumor cells use fatty acid rather than glucose as a fuel; the metabolic adaptation yields an insight into a novel platform for treating metastasis
Therapies targeting FAO and YAP are currently available or being actively developed. By drawing on the link between FAO /YAP and lymph node metastasis found by this study, doctors may be able to suppress subsequent distant metastasis in patients with melanoma and breast cancers.
science  medicine  cancer  lymph  metastasis  breast  melanoma 
february 2019 by emkay
skin cancer vs. sunscreen - the dilemma - grassrootshealth
"gorham presents 16 studies on sunscreen and melanoma risk – four studies found protective value to sunscreen; five studies had no conclusion; seven studies showed increased risk with use of sunscreen. [...] organized by latitude, these same studies show an increased risk of melanoma with sunscreen use for people with lighter pigmentation (northern latitudes); and no relationship with people of darker pigmentation (lower latitudes)."
skin-cancer  melanoma  sunscreen  health  vitamin-d  heliophobia  photoprotective-response  uv  uv-a  uv-b 
may 2018 by chl
RT : Yes!!! does your workplace also offer skin checks?? I seriously love this.
melanoma  from twitter
april 2018 by kcarruthers
Tumor mutational burden (TMB) correlates with T cell infiltration (CTL) in some tumors (, )
melanoma  LungCancer  from twitter_favs
april 2018 by maverickny
WOW! Dr Jeffrey S. Weber ROCKSTAR /alumn CRP at CA Pt values/Inhibi…
Immunotherapy  melanoma  from twitter_favs
march 2018 by maverickny

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