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

Article Article scientifique Article Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma eng 2016 author Bonilla Bustillo Ximena 739759 author Parmentier Laurent author King Bryan author Bezrukov Fedor 849834 author Kaya Guerkan 26603 author Zoete Vincent author Seplyarskiy Vladimir B author Sharpe Hayley J author Mckee Thomas Alexander 549937 author Letourneau Audrey 653025 author Ribaux Pascale Garlonne 543255 author Popadin Konstantin 736361 author Basset-Seguin Nicole author Chaabene Rouaa Ben author Santoni Federico 681638 author Andrianova Maria A author Guipponi Michel 118157 author Garieri Marco 794768 author Verdan Carole 94306 author Grosdemange Kerstin 125567 author Sumara Olga author Eilers Martin author Aifantis Iannis author Michielin Olivier author de Sauvage Frederic J author Antonarakis Stylianos 22813 author Nikolaev Sergey Igorievich 593779 398-406 10.1038/ng.3525 26950094 1061-4036 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. Dewey 576.5 Dewey 590 Dewey 616 Dewey 616.07 23 Institut de génétique et de génomique 0DH 135 Département de médecine génétique et développement 21D 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 false 476 Lymphomes MALT et réplication virale 807 196 Pathologie Moléculaire de la Trisomie 21 et le Génome Humain 248 478 Rôle du CD44 809 Nature genetics 48 4 570a9e72-183a-4794-9d59-56f961436052 Article (Accepted version) Restricted McKee T, Nat Genet, 2016, 48(4), 398-406.pdf 1595472 application/pdf restrictedAccess Centres et instituts / Institut de génétique et de génomique 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 Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma	Nature genetics			2016	877	8

Archive ouverte UNIGE

Verdan, Carole