Hafner, Christian and Toll, Agusti and Fernandez-Casado, Alejandro and Earl, Julie and Marques, Miriam and Acquadro, Francesco and Mendez-Pertuz, Marinela and Urioste, Miguel and Malats, Nuria and Burns, Julie E. and Knowles, Margaret A. and Cigudosa, Juan C. and Hartmann, Arndt and Vogt, Thomas and Landthaler, Michael and Pujol, Ramon M. and Real, Francisco X. (2010) Multiple oncogenic mutations and clonal relationship in spatially distinct benign human epidermal tumors. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107 (48). pp. 20780-20785. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about the genetic changes in benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal tumors without malignant potential. We performed a comprehensive mutational screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT pathways from 175 SK, including multiple lesions from each patient. SK commonly harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK and PI3K pathway signaling, we did not find induction of senescence or a DNA damage response. Array comparative genomic hybridization (aCGH) analysis revealed that SK are genetically stable. The pattern of oncogenic mutations and X chromosome inactivation departs significantly from randomness and indicates that spatially independent lesions from a given patient share a clonal relationship. Our findings show that multiple oncogenic mutations in the major signaling pathways involved in cancer are not sufficient to drive malignant tumor progression. Furthermore, our data provide clues on the origin and spread of oncogenic mutations in tissues, suggesting that apparently independent (multicentric) adult benign tumors may have a clonal origin.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR RECEPTOR-3; UROTHELIAL CELL-CARCINOMA; ACTIVATING MUTATIONS; INDUCED SENESCENCE; FGFR3 MUTATIONS; HUMAN SKIN; MYELOPROLIFERATIVE NEOPLASMS; THANATOPHORIC DYSPLASIA; CONFERS SUSCEPTIBILITY; SEBORRHEIC KERATOSIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2020 05:38 |
| Last Modified: | 07 Jul 2020 05:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23847 |
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