EGFR, PIK3CA, KRAS and BRAF mutations in meningiomas

Bujko,Mateusz; Kober,Paulina; Tysarowski,Andrzej; Matyja,Ewa; Mandat,Tomasz; Bonicki,Wiesław; Siedlecki,Janusz Aleksander

doi:10.3892/ol.2014.2042

EGFR, PIK3CA, KRAS and BRAF mutations in meningiomas

Authors:
- Mateusz Bujko
- Paulina Kober
- Andrzej Tysarowski
- Ewa Matyja
- Tomasz Mandat
- Wiesław Bonicki
- Janusz Aleksander Siedlecki
View Affiliations

Affiliations: Department of Molecular and Translational Oncology, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland, Department of Experimental and Clinical Neuropathology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw 02-106, Poland, Department of Neurosurgery, Maria Sklodowska‑Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland
Published online on: April 7, 2014 https://doi.org/10.3892/ol.2014.2042
Pages: 2019-2022

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Meningiomas are among the most frequent intracranial tumors. Treatment involves surgical resection with optional subsequent radiotherapy for high‑grade meningiomas or radiosurgery following incomplete tumor removal. At present, no pharmacological agents are used as treatment. The use of targeted therapies has been considered, and specific therapies, including anti‑EGFR treatment, have been clinically tested. The experience from the treatment of various types of cancers shows that patient outcome depends on the mutational status of particular molecules, including epithelial growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA). Therefore, the aim of the present study was to assess the occurrence and potential use of these markers in patients with meningioma. In total, 55 formalin‑fixed, paraffin‑embedded meningioma samples were subjected to genomic sequencing of EGFR (exons 18‑21), KRAS (exon 1), BRAF (exon 15) and PI3K (exons 9, 20). No mutations were identified in EGFR, KRAS or BRAF. Point mutations in PIK3CA were revealed in the samples of two patients with atypical and anaplastic meningiomas. Although these mutations appear to be rare, this result, along with previously reported findings, indicates that the PI3K/protein kinase B pathway may serve as a more reasonable molecular target for meningioma than EGFR.

View Figures

View References

1	Louis DN, Ohgaki H, Wiestler OD, et al: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114:97–109. 2007. View Article : Google Scholar : PubMed/NCBI
2	Normanno N, De Luca A, Bianco C, et al: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 366:2–16. 2006. View Article : Google Scholar : PubMed/NCBI
3	Torp SH, Helseth E, Dalen A and Unsgaard G: Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue. APMIS. 100:797–802. 1992. View Article : Google Scholar : PubMed/NCBI
4	Smith JS, Lal A, Harmon-Smith M, Bollen AW and McDermott MW: Association between absence of epidermal growth factor receptor immunoreactivity and poor prognosis in patients with atypical meningioma. J Neurosurg. 106:1034–1040. 2007. View Article : Google Scholar : PubMed/NCBI
5	Wernicke AG, Dicker AP, Whiton M, et al: Assessment of epidermal growth factor receptor (EGFR) expression in human meningioma. Radiat Oncol. 5:462010. View Article : Google Scholar : PubMed/NCBI
6	Carroll RS, Black PM, Zhang J, Kirsch M, Percec I, Lau N and Guha A: Expression and activation of epidermal growth factor receptors in meningiomas. J Neurosurg. 87:315–323. 1997. View Article : Google Scholar : PubMed/NCBI
7	Mawrin C, Sasse T, Kirches E, et al: Different activation of mitogen-activated protein kinase and Akt signaling is associated with aggressive phenotype of human meningiomas. Clin Cancer Res. 11:4074–4082. 2005. View Article : Google Scholar : PubMed/NCBI
8	Kargiotis O, Chetty C, Gogineni V, et al: uPA/uPAR downregulation inhibits radiation-induced migration, invasion and angiogenesis in IOMM-Lee meningioma cells and decreases tumor growth in vivo. Int J Oncol. 33:937–947. 2008.PubMed/NCBI
9	Johnson M and Toms S: Mitogenic signal transduction pathways in meningiomas: novel targets for meningioma chemotherapy? J Neuropathol Exp Neurol. 64:1029–1036. 2005. View Article : Google Scholar : PubMed/NCBI
10	Norden AD, Raizer JJ, Abrey LE, et al: Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol. 96:211–217. 2010. View Article : Google Scholar : PubMed/NCBI
11	Lynch TJ, Bell DW, Sordella R, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI
12	De Roock W, Claes B, Bernasconi D, et al: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 11:753–762. 2010.PubMed/NCBI
13	Brand TM, Iida M and Wheeler DL: Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol Ther. 11:777–792. 2011. View Article : Google Scholar : PubMed/NCBI
14	Samuels Y, Wang Z, Bardelli A, et al: High frequency of mutations of the PIK3CA gene in human cancers. Science. 304:5542004. View Article : Google Scholar : PubMed/NCBI
15	Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T and Mitsudomi T: Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 64:8919–8923. 2004. View Article : Google Scholar
16	Diedrich U, Lucius J, Baron E, Behnke J, Pabst B and Zoll B: Distribution of epidermal growth factor receptor gene amplification in brain tumours and correlation to prognosis. J Neurol. 242:683–688. 1995. View Article : Google Scholar : PubMed/NCBI
17	Chaffanet M, Chauvin C, Lainé M, et al: Comparative analysis of the NF2, TP53, PTEN, KRAS, NRAS and HRAS genes in sporadic and radiation-induced human meningiomas. Int J Cancer. 94:218–221. 2001. View Article : Google Scholar : PubMed/NCBI
18	Schindler G, Capper D, Meyer J, et al: Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 121:397–405. 2011. View Article : Google Scholar
19	Pang JC, Chung NY, Chan NH, Poon WS, Thomas T and Ng HK: Rare mutation of PIK3CA in meningiomas. Acta Neuropathol. 111:284–285. 2006. View Article : Google Scholar : PubMed/NCBI
20	Bader AG, Kang S and Vogt PK: Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci USA. 103:1475–1479. 2006. View Article : Google Scholar : PubMed/NCBI
21	Janku F, Wheler JJ, Naing A, et al: PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res. 73:276–284. 2013. View Article : Google Scholar : PubMed/NCBI
22	Peters N, Wellenreuther R, Rollbrocker B, Hayashi Y, Meyer-Puttlitz B, Duerr EM, Lenartz D, Marsh DJ, Schramm J, Wiestler OD, Parsons R, Eng C and von Deimling A: Analysis of the PTEN gene in human meningiomas. Neuropathol Appl Neurobiol. 24:3–8. 1998. View Article : Google Scholar
23	Willems L, Tamburini J, Chapuis N, Lacombe C, Mayeux P and Bouscary D: PI3K and mTOR signaling pathways in cancer: new data on targeted therapies. Curr Oncol Rep. 14:129–138. 2012. View Article : Google Scholar : PubMed/NCBI
24	Martini M, Ciraolo E, Gulluni F and Hirsch E: Targeting PI3K in cancer: Any good news? Front Oncology. 3:1082013. View Article : Google Scholar : PubMed/NCBI