Fibroblast growth factor family aberrations in cancers: Clinical and molecular characteristics
| Autor: | Richard Schwab, Teresa Helsten, Maria Schwaederle, Austin J. Parish, David Piccioni, Razelle Kurzrock, Paul T. Fanta, Kelly A. Shimabukuro, Gregory A. Daniels, BA Parker |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
animal structures Fibroblast Growth Factor Population Biology medicine.disease_cause Fibroblast growth factor Bioinformatics Metastasis Neoplasms Receptors medicine cancer FGF 2.1 Biological and endogenous factors Humans education Molecular Biology Aged education.field_of_study FGFR Fibroblast growth factor receptor 1 RPTOR Cell Biology sequencing Middle Aged medicine.disease Receptors Fibroblast Growth Factor cancer FGF FGFR sequencing profiling 4.1 Discovery and preclinical testing of markers and technologies Fibroblast Growth Factors Fibroblast growth factor receptor Chromosomal region embryonic structures Cancer research Female Biochemistry and Cell Biology profiling Carcinogenesis Developmental Biology Reports Signal Transduction |
| Zdroj: | Parish, A; Schwaederle, M; Daniels, G; Piccioni, D; Fanta, P; Schwab, R; et al.(2015). Fibroblast growth factor family aberrations in cancers: Clinical and molecular characteristics. Cell Cycle, 14(13), 2121-2128. doi: 10.1080/15384101.2015.1041691. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/9mg904cd Cell Cycle Cell cycle (Georgetown, Tex.), vol 14, iss 13 |
| DOI: | 10.1080/15384101.2015.1041691. |
| Popis: | © 2015 Taylor & Francis Group, LLC. Fibroblast growth factor ligands and receptors (FGF and FGFR) play critical roles in tumorigenesis, and several drugs have been developed to target them. We report the biologic correlates of FGF/FGFR abnormalities in diverse malignancies. The medical records of patients with cancers that underwent targeted next generation sequencing (182 or 236 cancer-related genes) were reviewed. The following FGF/FGFR genes were tested: FGF3, 4, 6, 7, 10, 12, 14, 19, 23 and FGFR1, 2, 3, and 4. Of 391 patients, 56 (14.3%) had aberrant FGF (N = 38, all amplifications) and/or FGFR (N = 22 including 5 mutations and one FGFR3-TACC3 fusion). FGF/FGFR aberrations were most frequent in breast cancers (26/81, 32.1%, p = 0.0003). In multivariate analysis, FGF/FGFR abnormalities were independently associated with CCND1/2, RICTOR, ZNF703, RPTOR, AKT2, and CDK8 alterations (all P < 0.02), as well as with an increased median number of alterations (P < 0.0001). FGF3, FGF4, FGF19 and CCND1 were co-amplified in 22 of 391 patients (5.6%, P < 0.0001), most likely because they co-localize on the same chromosomal region (11q13). There was no significant difference in time to metastasis or overall survival when comparing patients harboring FGF/FGFR alterations versus those not. Overall, FGF/FGFR was one of the most frequently aberrant pathways in our population comprising patients with diverse malignancies. These aberrations frequently co-exist with anomalies in a variety of other genes, suggesting that tailored combination therapy may be necessary in these patients. |
| Databáze: | OpenAIRE |
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