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Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets.
Newell, Felicity; Kong, Yan; Wilmott, James S; Johansson, Peter A; Ferguson, Peter M; Cui, Chuanliang; Li, Zhongwu; Kazakoff, Stephen H; Burke, Hazel; Dodds, Tristan J; Patch, Ann-Marie; Nones, Katia; Tembe, Varsha; Shang, Ping; van der Weyden, Louise; Wong, Kim; Holmes, Oliver; Lo, Serigne; Leonard, Conrad; Wood, Scott; Xu, Qinying; Rawson, Robert V; Mukhopadhyay, Pamela; Dummer, Reinhard; Levesque, Mitchell P; Jönsson, Göran; Wang, Xuan; Yeh, Iwei; Wu, Hong; Joseph, Nancy; Bastian, Boris C; Long, Georgina V; Spillane, Andrew J; Shannon, Kerwin F; Thompson, John F; Saw, Robyn P M; Adams, David J; Si, Lu; Pearson, John V; Hayward, Nicholas K; Waddell, Nicola; Mann, Graham J; Guo, Jun; Scolyer, Richard A.
Affiliation
  • Newell F; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Kong Y; Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • Wilmott JS; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Johansson PA; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Ferguson PM; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Cui C; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Li Z; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Kazakoff SH; Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • Burke H; Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • Dodds TJ; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Patch AM; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Nones K; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Tembe V; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Shang P; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • van der Weyden L; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Wong K; Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.
  • Holmes O; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Lo S; Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
  • Leonard C; Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
  • Wood S; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Xu Q; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Rawson RV; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Mukhopadhyay P; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Dummer R; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Levesque MP; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Jönsson G; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Wang X; Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.
  • Yeh I; QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Wu H; Dermatology Clinic, University Hospital Zürich, University of Zurich, Zurich, 8091, Switzerland.
  • Joseph N; Dermatology Clinic, University Hospital Zürich, University of Zurich, Zurich, 8091, Switzerland.
  • Bastian BC; Department of Oncology, Clinical Sciences, Lund University, Lund, 221 85, Sweden.
  • Long GV; Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • Spillane AJ; Departments of Dermatology and Pathology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, 94143, USA.
  • Shannon KF; Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
  • Thompson JF; Department of Pathology, University of California, San Francisco, CA, 94143, USA.
  • Saw RPM; Departments of Dermatology and Pathology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, 94143, USA.
  • Adams DJ; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Si L; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Pearson JV; Royal North Shore and Mater Hospitals, Sydney, NSW, 2065, Australia.
  • Hayward NK; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Waddell N; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Mann GJ; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
  • Guo J; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Scolyer RA; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, 2065, Australia.
Nat Commun ; 10(1): 3163, 2019 07 18.
Article in En | MEDLINE | ID: mdl-31320640
Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Point Mutation / Melanoma Limits: Female / Humans / Male Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Australia Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Tumor / Point Mutation / Melanoma Limits: Female / Humans / Male Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Australia Country of publication: United kingdom