Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma

Cancer Research
Kim ThraneJoakim Lundeberg

Abstract

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 tu...Continue Reading

Citations

Sep 2, 2019·Endocrine Pathology·Sunita M C De SousaHamish S Scott
May 12, 2019·Biology of Reproduction·Shinnosuke SuzukiBrian P Hermann
Mar 18, 2020·International Journal of Molecular Sciences·Arabel Vollmann-ZwerenzPeter Hau
Apr 23, 2020·Frontiers in Oncology·Guillermo de Anda-Jáuregui, Enrique Hernández-Lemus
Aug 15, 2020·Frontiers in Oncology·Natasja L de VriesNoel F C C de Miranda
Nov 27, 2020·Journal of the American Society of Nephrology : JASN·Christian HinzeKai M Schmidt-Ott
Feb 5, 2021·Journal of Clinical Medicine·Hans BinderManfred Kunz
Feb 16, 2021·Frontiers in Immunology·Violena PietrobonJakob Nikolas Kather
Mar 12, 2021·Bioinformatics·Alma Anderson, Joakim Lundeberg
Apr 4, 2021·Cancers·Yelyzaveta ShlyakhtinaMaximiliano M Portal
Apr 4, 2021·Cancer Discovery·L Nicolas Gonzalez CastroMario L Suvà
Feb 25, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Phillip M GalboDeyou Zheng
Jun 15, 2021·Frontiers in Oncology·Cristian ScatenaSara Tomei
Aug 10, 2021·GeroScience·Gerald S ShadelStefania Zambetti
Oct 9, 2021·Proceedings of the National Academy of Sciences of the United States of America·Deshka S FosterMichael T Longaker

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