| Literature DB >> 26950094 |
Ximena Bonilla1, Laurent Parmentier2, Bryan King3, Fedor Bezrukov4,5, Gürkan Kaya6, Vincent Zoete7, Vladimir B Seplyarskiy8,9,10, Hayley J Sharpe11, Thomas McKee12, Audrey Letourneau1, Pascale G Ribaux1, Konstantin Popadin1, Nicole Basset-Seguin13, Rouaa Ben Chaabene1, Federico A Santoni1,14, Maria A Andrianova8,9,10, Michel Guipponi14, Marco Garieri1, Carole Verdan12, Kerstin Grosdemange6, Olga Sumara15, Martin Eilers15,16, Iannis Aifantis3, Olivier Michielin7,17, Frederic J de Sauvage11, Stylianos E Antonarakis1,14,18, Sergey I Nikolaev1,14.
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.Entities:
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Year: 2016 PMID： 26950094 DOI： 10.1038/ng.3525
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330