Anne Zaremba1, Rajmohan Murali2, Philipp Jansen1, Inga Möller1, Antje Sucker1, Annette Paschen1, Lisa Zimmer1, Elisabeth Livingstone1, Titus J Brinker3, Eva Hadaschik1, Cindy Franklin4, Alexander Roesch1, Selma Ugurel1, Dirk Schadendorf1, Klaus G Griewank5, Ioana Cosgarea6. 1. Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany. 2. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Dermatology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Disease (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany. 4. Department of Dermatology and Venerology, University of Cologne, Cologne, Germany. 5. Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany; Dermatopathologie bei Mainz, Nieder-Olm, Germany. 6. Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany; Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address: Ioana.cosgarea@newcastle.ac.uk.
Abstract
STUDY AIM: Melanomas arising in acral sites are associated with a poorer prognosis than other melanoma subtypes. The aim of this study was to evaluate clinical-pathological and genetic characteristics as well as therapeutic responses of a larger cohort of patients with melanomas arising in acral sites. METHODS: Clinical data of 134 patients with melanomas arising in acral sites from the Dept. of Dermatology Essen were collected and analysed with regard to clinicopathological characteristics and treatment responses. Genetic analysis with targeted next-generation sequencing was done on 50 samples. RESULTS: In our cohort, BRAF (30%), NRAS (28%), TERT promoter (26%), NF1 (14%) and KIT (6%) were frequently identified mutations. Comparing tumours situated on palms and soles with melanomas arising on dorsal acral sites, a higher frequency of NRAS (39.1% versus 25%) and NF1 (17.3% versus 0%) and lower frequencies of BRAF (21.7% versus 75%) and TERT promoter (8.6% versus 50%) mutations were observed. MAPK activating mutations were identified in 64% of tumours. Overall survival was longer in patients treated with immune checkpoint inhibitors as first-line treatment than in patients receiving other systemic therapies (i.e. BRAF/MEK inhibitors and chemotherapy). CONCLUSION: Our data suggest that the genetics of melanomas arising in acral sites varies by tumour location and may influence biological behaviour.
STUDY AIM: Melanomas arising in acral sites are associated with a poorer prognosis than other melanoma subtypes. The aim of this study was to evaluate clinical-pathological and genetic characteristics as well as therapeutic responses of a larger cohort of patients with melanomas arising in acral sites. METHODS: Clinical data of 134 patients with melanomas arising in acral sites from the Dept. of Dermatology Essen were collected and analysed with regard to clinicopathological characteristics and treatment responses. Genetic analysis with targeted next-generation sequencing was done on 50 samples. RESULTS: In our cohort, BRAF (30%), NRAS (28%), TERT promoter (26%), NF1 (14%) and KIT (6%) were frequently identified mutations. Comparing tumours situated on palms and soles with melanomas arising on dorsal acral sites, a higher frequency of NRAS (39.1% versus 25%) and NF1 (17.3% versus 0%) and lower frequencies of BRAF (21.7% versus 75%) and TERT promoter (8.6% versus 50%) mutations were observed. MAPK activating mutations were identified in 64% of tumours. Overall survival was longer in patients treated with immune checkpoint inhibitors as first-line treatment than in patients receiving other systemic therapies (i.e. BRAF/MEK inhibitors and chemotherapy). CONCLUSION: Our data suggest that the genetics of melanomas arising in acral sites varies by tumour location and may influence biological behaviour.
Authors: Genevieve J Kaunitz; Tricia R Cottrell; Mohammed Lilo; Valliammai Muthappan; Jessica Esandrio; Sneha Berry; Haiying Xu; Aleksandra Ogurtsova; Robert A Anders; Alexander H Fischer; Stefan Kraft; Meg R Gerstenblith; Cheryl L Thompson; Kord Honda; Jonathan D Cuda; Charles G Eberhart; James T Handa; Evan J Lipson; Janis M Taube Journal: Lab Invest Date: 2017-07-24 Impact factor: 5.662
Authors: Y Teramoto; U Keim; A Gesierich; G Schuler; E Fiedler; T Tüting; C Ulrich; U Wollina; J C Hassel; R Gutzmer; S Goerdt; C Zouboulis; U Leiter; T K Eigentler; C Garbe Journal: Br J Dermatol Date: 2017-12-20 Impact factor: 9.302
Authors: Caroline Robert; Jacob Schachter; Georgina V Long; Ana Arance; Jean Jacques Grob; Laurent Mortier; Adil Daud; Matteo S Carlino; Catriona McNeil; Michal Lotem; James Larkin; Paul Lorigan; Bart Neyns; Christian U Blank; Omid Hamid; Christine Mateus; Ronnie Shapira-Frommer; Michele Kosh; Honghong Zhou; Nageatte Ibrahim; Scot Ebbinghaus; Antoni Ribas Journal: N Engl J Med Date: 2015-04-19 Impact factor: 91.245
Authors: Alexandra M Haugh; Bin Zhang; Victor L Quan; Erin M Garfield; Jeffrey A Bubley; Emily Kudalkar; Anna Elisa Verzi; Kara Walton; Timothy VandenBoom; Emily A Merkel; Christina Y Lee; Timothy Tan; Maria Cristina Isales; Betty Y Kong; Alexander T Wenzel; Christopher G Bunick; Jaehyuk Choi; Jeffrey Sosman; Pedram Gerami Journal: J Invest Dermatol Date: 2017-09-01 Impact factor: 8.551
Authors: James Larkin; Vanna Chiarion-Sileni; Rene Gonzalez; Jean Jacques Grob; C Lance Cowey; Christopher D Lao; Dirk Schadendorf; Reinhard Dummer; Michael Smylie; Piotr Rutkowski; Pier F Ferrucci; Andrew Hill; John Wagstaff; Matteo S Carlino; John B Haanen; Michele Maio; Ivan Marquez-Rodas; Grant A McArthur; Paolo A Ascierto; Georgina V Long; Margaret K Callahan; Michael A Postow; Kenneth Grossmann; Mario Sznol; Brigitte Dreno; Lars Bastholt; Arvin Yang; Linda M Rollin; Christine Horak; F Stephen Hodi; Jedd D Wolchok Journal: N Engl J Med Date: 2015-05-31 Impact factor: 91.245
Authors: Adil I Daud; Jedd D Wolchok; Caroline Robert; Wen-Jen Hwu; Jeffrey S Weber; Antoni Ribas; F Stephen Hodi; Anthony M Joshua; Richard Kefford; Peter Hersey; Richard Joseph; Tara C Gangadhar; Roxana Dronca; Amita Patnaik; Hassane Zarour; Charlotte Roach; Grant Toland; Jared K Lunceford; Xiaoyun Nicole Li; Kenneth Emancipator; Marisa Dolled-Filhart; S Peter Kang; Scot Ebbinghaus; Omid Hamid Journal: J Clin Oncol Date: 2016-10-31 Impact factor: 44.544
Authors: Jason Madore; Ricardo E Vilain; Alexander M Menzies; Hojabr Kakavand; James S Wilmott; Jessica Hyman; Jennifer H Yearley; Richard F Kefford; John F Thompson; Georgina V Long; Peter Hersey; Richard A Scolyer Journal: Pigment Cell Melanoma Res Date: 2014-12-22 Impact factor: 4.693
Authors: Eliezer M Van Allen; Nikhil Wagle; Antje Sucker; Daniel J Treacy; Cory M Johannessen; Eva M Goetz; Chelsea S Place; Amaro Taylor-Weiner; Steven Whittaker; Gregory V Kryukov; Eran Hodis; Mara Rosenberg; Aaron McKenna; Kristian Cibulskis; Deborah Farlow; Lisa Zimmer; Uwe Hillen; Ralf Gutzmer; Simone M Goldinger; Selma Ugurel; Helen J Gogas; Friederike Egberts; Carola Berking; Uwe Trefzer; Carmen Loquai; Benjamin Weide; Jessica C Hassel; Stacey B Gabriel; Scott L Carter; Gad Getz; Levi A Garraway; Dirk Schadendorf Journal: Cancer Discov Date: 2013-11-21 Impact factor: 39.397
Authors: Carl M Thielmann; Eleftheria Chorti; Johanna Matull; Rajmohan Murali; Anne Zaremba; Georg Lodde; Philipp Jansen; Luisa Richter; Julia Kretz; Inga Möller; Antje Sucker; Rudolf Herbst; Patrick Terheyden; Jochen Utikal; Claudia Pföhler; Jens Ulrich; Alexander Kreuter; Peter Mohr; Ralf Gutzmer; Friedegund Meier; Edgar Dippel; Michael Weichenthal; Annette Paschen; Elisabeth Livingstone; Lisa Zimmer; Dirk Schadendorf; Eva Hadaschik; Selma Ugurel; Klaus G Griewank Journal: Eur J Cancer Date: 2021-11-04 Impact factor: 10.002
Authors: Carl Maximilian Thielmann; Johanna Matull; Sebastian Roth; Jan-Malte Placke; Eleftheria Chorti; Anne Zaremba; Georg Lodde; Philipp Jansen; Frederik Krefting; Julia Kretz; Inga Möller; Antje Sucker; Annette Paschen; Elisabeth Livingstone; Lisa Zimmer; Selma Ugurel; Dirk Schadendorf; Eva Hadaschik; Klaus G Griewank Journal: Cancers (Basel) Date: 2022-04-22 Impact factor: 6.575
Authors: Xiaoting Wei; Di Wu; Hang Li; Rui Zhang; Yu Chen; Hong Yao; Zhihong Chi; Xinan Sheng; Chuanliang Cui; Xue Bai; Zhonghui Qi; Ke Li; Shijie Lan; Lizhu Chen; Rui Guo; Xinyu Yao; Lili Mao; Bin Lian; Yan Kong; Jie Dai; Bixia Tang; Xieqiao Yan; Xuan Wang; Siming Li; Li Zhou; Charles M Balch; Lu Si; Jun Guo Journal: Ann Surg Oncol Date: 2020-04-06 Impact factor: 5.344
Authors: Sara S Bernardes; Ingrid Ferreira; David E Elder; Aretha B Nobre; Héctor Martínez-Said; David J Adams; Carla Daniela Robles-Espinoza; Patricia A Possik Journal: J Pathol Clin Res Date: 2021-07-02