Journal article
Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma.
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Bonilla X
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Parmentier L
Department of Dermatology, Hospital of Valais, Sierre, Switzerland.
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King B
Department of Pathology, New York University School of Medicine, New York, New York, USA.
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Bezrukov F
Department of Physics, University of Connecticut, Storrs, Connecticut, USA.
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Kaya G
Department of Dermatology, University Hospitals of Geneva, Geneva, Switzerland.
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Zoete V
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
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Seplyarskiy VB
Institute of Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia.
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Sharpe HJ
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California, USA.
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McKee T
Service of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland.
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Letourneau A
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Ribaux PG
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Popadin K
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Basset-Seguin N
Department of Dermatology, Saint Louis Hospital, Paris 7 University, Paris, France.
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Ben Chaabene R
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Santoni FA
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Andrianova MA
Institute of Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia.
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Guipponi M
Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
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Garieri M
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Verdan C
Service of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland.
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Grosdemange K
Department of Dermatology, University Hospitals of Geneva, Geneva, Switzerland.
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Sumara O
Department of Biochemistry and Molecular Biology, University of Würzburg, Würzburg, Germany.
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Eilers M
Department of Biochemistry and Molecular Biology, University of Würzburg, Würzburg, Germany.
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Aifantis I
Department of Pathology, New York University School of Medicine, New York, New York, USA.
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Michielin O
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
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de Sauvage FJ
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California, USA.
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Antonarakis SE
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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Nikolaev SI
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
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English
Basal cell carcinoma (BCC) of the skin is the most common malignant neoplasm in humans. BCC is primarily driven by the Sonic Hedgehog (Hh) pathway. However, its phenotypic variation remains unexplained. Our genetic profiling of 293 BCCs found the highest mutation rate in cancer (65 mutations/Mb). Eighty-five percent of the BCCs harbored mutations in Hh pathway genes (PTCH1, 73% or SMO, 20% (P = 6.6 × 10(-8)) and SUFU, 8%) and in TP53 (61%). However, 85% of the BCCs also harbored additional driver mutations in other cancer-related genes. We observed recurrent mutations in MYCN (30%), PPP6C (15%), STK19 (10%), LATS1 (8%), ERBB2 (4%), PIK3CA (2%), and NRAS, KRAS or HRAS (2%), and loss-of-function and deleterious missense mutations were present in PTPN14 (23%), RB1 (8%) and FBXW7 (5%). Consistent with the mutational profiles, N-Myc and Hippo-YAP pathway target genes were upregulated. Functional analysis of the mutations in MYCN, PTPN14 and LATS1 suggested their potential relevance in BCC tumorigenesis.
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Language
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Open access status
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closed
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/118429
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