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

Ximena Bonilla; Laurent Parmentier; Bryan King; Fedor Bezrukov; Gürkan Kaya; Vincent Zoete; Vladimir B. Seplyarskiy; Hayley J. Sharpe; Thomas McKee; Audrey Letourneau; Pascale G. Ribaux; Konstantin Popadin; Nicole Basset-Seguin; Rouaa Ben Chaabene; Federico A. Santoni; Maria A. Andrianova; Michel Guipponi; Marco Garieri; Carole Verdan; Kerstin Grosdemange; Olga Sumara; Martin Eilers; Iannis Aifantis; Olivier Michielin; Frederic J. De Sauvage; Stylianos E. Antonarakis; Sergey I. Nikolaev

doi:10.1038/ng.3525

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

Ximena Bonilla, Laurent Parmentier, Bryan King, Fedor Bezrukov, Gürkan Kaya, Vincent Zoete, Vladimir B. Seplyarskiy, Hayley J. Sharpe, Thomas McKee, Audrey Letourneau, Pascale G. Ribaux, Konstantin Popadin, Nicole Basset-Seguin, Rouaa Ben Chaabene, Federico A. Santoni, Maria A. Andrianova, Michel Guipponi, Marco Garieri, Carole Verdan, Kerstin GrosdemangeOlga Sumara, Martin Eilers, Iannis Aifantis, Olivier Michielin, Frederic J. De Sauvage, Stylianos E. Antonarakis, Sergey I. Nikolaev

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

359 Citations (Scopus)

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.

langue originale	Anglais
Pages (de - à)	398-406
Nombre de pages	9
journal	Nature Genetics
Volume	48
Numéro de publication	4
Les DOIs	https://doi.org/10.1038/ng.3525
état	Publié - 29 mars 2016
Modification externe	Oui

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10.1038/ng.3525

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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., Chaabene, R. B., Santoni, F. A., Andrianova, M. A., Guipponi, M., Garieri, M., Verdan, C., ... Nikolaev, S. I. (2016). Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nature Genetics, 48(4), 398-406. https://doi.org/10.1038/ng.3525

@article{1e1bd3f0bbe34d8aa9245f5a52b3251d,

title = "Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma",

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.",

author = "Ximena Bonilla and Laurent Parmentier and Bryan King and Fedor Bezrukov and G{\"u}rkan Kaya and Vincent Zoete and Seplyarskiy, {Vladimir B.} and Sharpe, {Hayley J.} and Thomas McKee and Audrey Letourneau and Ribaux, {Pascale G.} and Konstantin Popadin and Nicole Basset-Seguin and Chaabene, {Rouaa Ben} and Santoni, {Federico A.} and Andrianova, {Maria A.} and Michel Guipponi and Marco Garieri and Carole Verdan and Kerstin Grosdemange and Olga Sumara and Martin Eilers and Iannis Aifantis and Olivier Michielin and {De Sauvage}, {Frederic J.} and Antonarakis, {Stylianos E.} and Nikolaev, {Sergey I.}",

note = "Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",

year = "2016",

month = mar,

day = "29",

doi = "10.1038/ng.3525",

language = "English",

volume = "48",

pages = "398--406",

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Bonilla, X, Parmentier, L, King, B, Bezrukov, F, Kaya, G, Zoete, V, Seplyarskiy, VB, Sharpe, HJ, McKee, T, Letourneau, A, Ribaux, PG, Popadin, K, Basset-Seguin, N, Chaabene, RB, Santoni, FA, Andrianova, MA, Guipponi, M, Garieri, M, Verdan, C, Grosdemange, K, Sumara, O, Eilers, M, Aifantis, I, Michielin, O, De Sauvage, FJ, Antonarakis, SE & Nikolaev, SI 2016, 'Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma', Nature Genetics, VOL. 48, Numéro 4, p. 398-406. https://doi.org/10.1038/ng.3525

TY - JOUR

T1 - Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma

AU - Bonilla, Ximena

AU - Parmentier, Laurent

AU - King, Bryan

AU - Bezrukov, Fedor

AU - Kaya, Gürkan

AU - Zoete, Vincent

AU - Seplyarskiy, Vladimir B.

AU - Sharpe, Hayley J.

AU - McKee, Thomas

AU - Letourneau, Audrey

AU - Ribaux, Pascale G.

AU - Popadin, Konstantin

AU - Basset-Seguin, Nicole

AU - Chaabene, Rouaa Ben

AU - Santoni, Federico A.

AU - Andrianova, Maria A.

AU - Guipponi, Michel

AU - Garieri, Marco

AU - Verdan, Carole

AU - Grosdemange, Kerstin

AU - Sumara, Olga

AU - Eilers, Martin

AU - Aifantis, Iannis

AU - Michielin, Olivier

AU - De Sauvage, Frederic J.

AU - Antonarakis, Stylianos E.

AU - Nikolaev, Sergey I.

PY - 2016/3/29

Y1 - 2016/3/29

N2 - 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.

AB - 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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