Journal article
A Transposon-Based Analysis of Gene Mutations Related to Skin Cancer Development
Journal of investigative dermatology, Vol.133(1), pp.239-248
01/2013
DOI: 10.1038/jid.2012.245
PMID: 22832494
Abstract
Nonmelanoma skin cancer (NMSC) is by far the most frequent type of cancer in humans. NMSC includes several types of malignancies with different clinical outcomes, the most frequent being basal and squamous cell carcinomas. We have used the Sleeping Beauty transposon/transposase system to identify somatic mutations associated with NMSC. Transgenic mice bearing multiple copies of a mutagenic Sleeping Beauty transposon T2Onc2 and expressing the SB11 transposase under the transcriptional control of regulatory elements from the keratin K5 promoter were treated with TPA, either in wild-type or Ha-ras mutated backgrounds. After several weeks of treatment, mice with transposition developed more malignant tumors with decreased latency compared with control mice. Transposon/transposase animals also developed basal cell carcinomas. Genetic analysis of the transposon integration sites in the tumors identified several genes recurrently mutated in different tumor samples, which may represent novel candidate cancer genes. We observed alterations in the expression levels of some of these genes in human tumors. Our results show that inactivating mutations in Notch1 and Nsd1, among others, may have an important role in skin carcinogenesis.
Details
- Title: Subtitle
- A Transposon-Based Analysis of Gene Mutations Related to Skin Cancer Development
- Creators
- Rita M Quintana - Department of Molecular Oncology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainAdam J Dupuy - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAAna Bravo - Department of Veterinary Clinical Sciences, Laboratory of Pathology Phenotyping of Genetically Engineered Mice, Faculty of Veterinary Medicine, University of Santiago de Compostela, Lugo, SpainM Llanos Casanova - Department of Molecular Oncology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainJosefa P Alameda - Department of Molecular Oncology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainAngustias Page - Department of Molecular Oncology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainMiguel Sánchez-Viera - IDEI, Institute for Dermatology, Aging and Cancer, Madrid, SpainAngel Ramírez - Department of Molecular Oncology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainManuel Navarro - Department of Molecular Oncology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.133(1), pp.239-248
- Publisher
- Elsevier Inc
- DOI
- 10.1038/jid.2012.245
- PMID
- 22832494
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Language
- English
- Date published
- 01/2013
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025470802771
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