Anatomic position determines oncogenic specificity in melanoma.

Autor: Weiss JM; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cell and Developmental Biology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA., Hunter MV; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Cruz NM; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Baggiolini A; Developmental Biology, The Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Tagore M; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ma Y; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cell and Developmental Biology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA., Misale S; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Marasco M; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Simon-Vermot T; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Campbell NR; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Physiology, Biophysics & Systems Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA., Newell F; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Wilmott JS; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia., Johansson PA; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Thompson JF; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Royal Prince Alfred Hospital, Sydney, New South Wales, Australia., Long GV; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Royal North Shore Hospital, Sydney, New South Wales, Australia., Pearson JV; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Mann GJ; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.; John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia.; Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, Sydney, New South Wales, Australia., Scolyer RA; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.; New South Wales Health Pathology, Sydney, New South Wales, Australia., Waddell N; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia., Montal ED; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Huang TH; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jonsson P; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Donoghue MTA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Harris CC; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Taylor BS; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Xu T; Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chaligné R; Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Shliaha PV; Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark.; Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hendrickson R; Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jungbluth AA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lezcano C; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Koche R; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Studer L; Developmental Biology, The Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ariyan CE; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Solit DB; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wolchok JD; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.; Weill Cornell Medicine, New York, NY, USA., Merghoub T; Weill Cornell Medicine, New York, NY, USA., Rosen N; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hayward NK; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., White RM; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. whiter@mskcc.org.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Apr; Vol. 604 (7905), pp. 354-361. Date of Electronic Publication: 2022 Mar 30.
DOI: 10.1038/s41586-022-04584-6
Abstrakt: Oncogenic alterations to DNA are not transforming in all cellular contexts 1,2 . This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails 3 . We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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