| Title | Highly Prevalent Genetic Alterations in Receptor Tyrosine Kinases and PI3K/Akt and MAP Kinase Pathways in Anaplastic and Follicular Thyroid Cancers. | | Author(s) | Liu Z, Hou P, Ji M, Guan H, Studeman K, Jensen K, Vasko V, El-Naggar AK, Xing M | | Institution | Division of Endocrinology and Metabolism, the Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD 20814; Department of Pathology, MD Anderson Cancer Center, Houston, TX 77030. | | Source | J Clin Endocrinol Metab 2008 May 20. | | Abstract | Context. Genetic alterations in receptor tyrosine kinases (RTKs) and PI3K/Akt and MAP kinase pathways have not been fully defined in anaplastic and follicular thyroid cancers (ATC, FTC).
Objective. To explore a wide-range genetic basis for the involvement of these pathways in ATC. Design. We examined mutations and copy number gains of a large panel of genes in these pathways and corresponding phosphorylation of Akt (p-Akt) and ERK (p-ERK).
Results. We found frequent copy gains of RTK genes, including EGFR, PDGFRalpha and beta, VEGFR1 and 2, KIT and MET, and in PIK3Ca, PIK3Cb and PDK1 genes in the PI3K/Akt pathway. Mutations of Ras, PIK3Ca, PTEN, and BRAF genes and RET/PTC rearrangements were common while mutations in PDK1, Akt1, Akt2, and RTK genes were uncommon in ATC. Overall, 46/48 (95.8%) ATC harbored at least one genetic alteration and co-existence of two or more was seen in 37/48 (77.1%) ATC. These genetic alterations were somewhat less common in FTC. Genetic alterations that could activate both the PI3K/Akt and MAP kinase pathways were found in 39/48 (81.3%) ATC. RTK gene copy gains were preferentially associated with p-Akt, suggesting their dominant role in activating the PI3K/Akt pathway. p-Akt was far more common than p-ERK in FTC, and both were relatively common and often co-existed in ATC.
Conclusions. Genetic alterations in the RTKs and PI3K/Akt and MAP kinase pathways are extremely prevalent in ATC and FTC, providing a strong genetic basis for an extensive role of these signaling pathways and for the development of therapies targeting these pathways for ATC and FTC, particularly the former. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18492751 |
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