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

Détails

ID Serval
serval:BIB_8EDEF7DDCC06
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma.
Périodique
Nature Genetics
Auteur⸱e⸱s
Bonilla X., Parmentier L., King B., Bezrukov F., Kaya G., Zoete V., Seplyarskiy V.B., Sharpe H.J., McKee T., Letourneau A., Ribaux P.G., Popadin K., Basset-Seguin N., Ben Chaabene R., Santoni F.A., Andrianova M.A., Guipponi M., Garieri M., Verdan C., Grosdemange K., Sumara O., Eilers M., Aifantis I., Michielin O., de Sauvage F.J., Antonarakis S.E., Nikolaev S.I.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
48
Numéro
4
Pages
398-406
Langue
anglais
Résumé
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.
Mots-clé
Anilides/therapeutic use, Antineoplastic Agents/therapeutic use, Carcinogenesis/genetics, Carcinoma, Basal Cell/drug therapy, Carcinoma, Basal Cell/genetics, DNA Mutational Analysis, Disease Progression, Exome, Genetic Association Studies, Genetic Predisposition to Disease, HEK293 Cells, Humans, Mutation, Pyridines/therapeutic use, Signal Transduction/radiation effects, Skin Neoplasms/drug therapy, Skin Neoplasms/genetics, Transcriptome
Pubmed
Web of science
Création de la notice
10/03/2016 18:15
Dernière modification de la notice
20/08/2019 14:52
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