title: Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma.
abstract: Mouse models of cancers are routinely used to study cancer biology. However, it remains unclear whether carcinogenesis in mice is driven by the same spectrum of genomic alterations found in humans. Here we conducted a comprehensive genomic analysis of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced skin cancer, the most commonly used skin cancer model, which appears as benign papillomas that progress into squamous cell carcinomas (SCCs). We also studied genetically induced SCCs that expressed G12D mutant Kras (Kras G12D) but were deficient for p53. Using whole-exome sequencing, we uncovered a characteristic mutational signature of DMBA-induced SCCs. We found that the vast majority of DMBA-induced SCCs presented recurrent mutations in Hras, Kras or Rras2 and mutations in several additional putative oncogenes and tumor-suppressor genes. Similar genes were recurrently mutated in mouse and human SCCs that were from different organs or had been exposed to different carcinogens. Invasive SCCs, but not papillomas, presented substantial chromosomal aberrations, especially in DMBA-induced and genetically induced Trp53-mutated SCCs. Metastasis occurred through sequential spreading, with relatively few additional genetic events. This study provides a framework for future functional cancer genomic studies in mice.
authors.affiliation: Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), Université libre de Buxelles (ULB), Brussels, Belgium.
authors.forename: Dany
authors.initials: D
authors.lastname: Nassar
authors.affiliation: Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), Université libre de Buxelles (ULB), Brussels, Belgium.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Latil
authors.affiliation: 1] Vesalius Research Center, Vlaams Instituut voor Biotechnologie VIB, Leuven, Belgium. [2] Laboratory for Translational Genetics, Department of Oncology, Katholieke Universiteit Leuven (KUL), Leuven, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Boeckx
authors.affiliation: 1] Vesalius Research Center, Vlaams Instituut voor Biotechnologie VIB, Leuven, Belgium. [2] Laboratory for Translational Genetics, Department of Oncology, Katholieke Universiteit Leuven (KUL), Leuven, Belgium.
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.affiliation: 1] Institut de recherche interdisciplinaire en biologie humaine et moléculaire (IRIBHM), Université libre de Buxelles (ULB), Brussels, Belgium. [2] WELBIO, Brussels, Belgium.
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D060965:Clonal Evolution; D059472:Exome; D005260:Female; D011905:Genes, ras; D023281:Genomics; D006801:Humans; D051379:Mice; D009154:Mutation; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene