Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma

Bonilla Bustillo, Ximena; Parmentier, Laurent; King, Bryan; Bezrukov, Fedor; Kaya, Gurkan; Zoete, Vincent; Seplyarskiy, Vladimir B; Sharpe, Hayley J; Mckee, Thomas Alexander; Letourneau, Audrey; Ribaux, Pascale Garlonne; Popadin, Konstantin; Basset-Seguin, Nicole; Chaabene, Rouaa Ben; Santoni, Federico; Andrianova, Maria A; Guipponi, Michel; Garieri, Marco; Verdan, Carole; Grosdemange, Kerstin; Sumara, Olga; Eilers, Martin; Aifantis, Iannis; Michielin, Olivier; de Sauvage, Frederic J; Antonarakis, Stylianos; Nikolaev, Sergey Igorievich

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Title		Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma
Authors		Bonilla Bustillo, Ximena Parmentier, Laurent King, Bryan Bezrukov, Fedor Kaya, Gurkan Zoete, Vincent Seplyarskiy, Vladimir B Sharpe, Hayley J Mckee, Thomas Alexander Letourneau, Audrey Ribaux, Pascale Garlonne Popadin, Konstantin Basset-Seguin, Nicole Chaabene, Rouaa Ben Santoni, Federico Andrianova, Maria A Guipponi, Michel Garieri, Marco Verdan, Carole Grosdemange, Kerstin Sumara, Olga Eilers, Martin Aifantis, Iannis Michielin, Olivier de Sauvage, Frederic J Antonarakis, Stylianos Nikolaev, Sergey Igorievich show all authors [1 - 27]
Published in		Nature Genetics. 2016, vol. 48, no. 4, p. 398-406
Abstract		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.
Identifiers		DOI: 10.1038/ng.3525 PMID: 26950094
Full text		Article (Author postprint) (1.5 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Centres et instituts / Institut de génétique et de génomique
Research groups		Lymphomes MALT et réplication virale (807) Rôle du CD44 (809) Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Citation (ISO format)		BONILLA BUSTILLO, Ximena et al. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. In: Nature Genetics, 2016, vol. 48, n° 4, p. 398-406. https://archive-ouverte.unige.ch/unige:84469