Home Medicine Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models
Article
Licensed
Unlicensed Requires Authentication

Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models

  • Juan Pedro Martinez-Barbera EMAIL logo and Rolf Buslei EMAIL logo
Published/Copyright: December 11, 2014
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 1-2

Abstract

Adamantinomatous craniopharyngiomas (ACPs) are histologically benign but clinically aggressive epithelial tumours of the sellar region that are associated with high morbidity and occasional mortality. Research from the last 3 years has provided important insights into the molecular and cellular pathogenesis of these tumours. It has become established that mutations in CTNNB1 (encoding β-catenin), leading to the over-activation of the WNT pathway, underlie the molecular aetiology of human ACP. Interestingly, the effect of these mutations is restricted to a small number of tumour cells, mostly forming clusters, which recent research has shown to be critical for tumorigenesis in mice and humans. Several pathways have been found to be activated in these clusters including the epidermal growth factor receptor and the sonic hedgehog pathways, offering potential therapeutic targets. A novel and unexpected role for pituitary stem cells has been proposed, which is fundamentally distinct from the cancer stem cell paradigm. The study of these benign tumours could reveal important insights into general mechanisms underlying the initial steps of tumorigenesis and facilitate novel tools to improve managements of the patients.

Keywords: beta-catenin; craniopharyngioma; EGFR; mouse models; pituitary; sonic hedgehog; stem cells; tumours
Corresponding authors: Dr. Juan Pedro Martinez-Barbera, Birth Defects Research Centre, Developmental Biology and Cancer Programme, Institute of Child Health, University College London, 30 Guilford Street, WC1N 1EH London, UK, E-mail: ; and Rolf Buslei, Department of Neuropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054 Erlangen, Germany, E-mail:

Acknowledgments

We are grateful to Dr. Andoniadou for comments on the manuscript. This work was supported by grants: W1055 from Children with Cancer UK (CWCUK) and Great Ormond Street Hospital Children’s Charity (GOSHCC) and 164126 from the Medical Research Council (MRC).

References

1. Nielsen EH, Feldt-Rasmussen U, Poulsgaard L, Kristensen LO, Astrup J, et al. Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults. J Neurooncol 2011;104:755–63.10.1007/s11060-011-0540-6Search in Google Scholar PubMed

2. Muller HL. Craniopharyngioma. Endocr Rev 2014:35;513–43.10.1210/er.2013-1115Search in Google Scholar PubMed

3. Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, et al. International Society of Neuropathology-Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 2014;24:429–35.10.1111/bpa.12171Search in Google Scholar PubMed PubMed Central

4. Holsken A, Buchfelder M, Fahlbusch R, Blümcke I, Buslei R. Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling. Acta Neuropathol 2010;119:631–9.10.1007/s00401-010-0642-9Search in Google Scholar PubMed

5. Aquilina K, Merchant TE, Rodriguez-Galindo C, Ellison DW, Sanford RA, et al. Malignant transformation of irradiated craniopharyngioma in children: report of 2 cases. J Neurosurg Pediatr 2010;5:155–61.10.3171/2009.9.PEDS09257Search in Google Scholar PubMed

6. Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet 2014;46:161–5.10.1038/ng.2868Search in Google Scholar PubMed PubMed Central

7. Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, et al. The descriptive epidemiology of craniopharyngioma. J Neurosurg 1998;89:547–51.10.3171/jns.1998.89.4.0547Search in Google Scholar PubMed

8. Karavitaki N, Brufani C, Warner JT, Adams CB, Richards P, et al. Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up. Clin Endocrinol (Oxf) 2005;62:397–409.10.1111/j.1365-2265.2005.02231.xSearch in Google Scholar PubMed

9. Muller HL. Childhood craniopharyngioma: current controversies on management in diagnostics, treatment and follow-up. Exp Rev Neurother 2010;10:515–24.10.1586/ern.10.15Search in Google Scholar PubMed

10. Young SC, Zimmerman RA, Nowell MA, Bilaniuk LT, Hackney DB, et al. Giant cystic craniopharyngiomas. Neuroradiology 1987;29:468–73.10.1007/BF00341745Search in Google Scholar PubMed

11. Pettorini BL, Inzitari R, Massimi L, Tamburrini G, Caldarelli M, et al. The role of inflammation in the genesis of the cystic component of craniopharyngiomas. Childs Nerv Syst 2010;26: 1779–84.10.1007/s00381-010-1245-4Search in Google Scholar

12. Desiderio C, Martelli C, Rossetti DV, Di Rocco C, D’Angelo L, et al. Identification of thymosins beta4 and beta 10 in paediatric craniopharyngioma cystic fluid. Childs Nerv Syst 2013;29: 951–60.10.1007/s00381-013-2069-9Search in Google Scholar

13. Martelli C, Iavarone F, Vincenzoni F, Rossetti DV, D’Angelo L, et al. Proteomic characterization of pediatric craniopharyngioma intracystic fluid by LC-MS top-down/bottom-up integrated approaches. Electrophoresis 2014;35:2172–83.10.1002/elps.201300578Search in Google Scholar

14. Sekine S, Sato S, Takata T, Fukuda Y, Ishida T, et al. Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas. Am J Pathol 2003;163:1707–12.10.1016/S0002-9440(10)63528-6Search in Google Scholar

15. Ahn SG, Kim SA, Kim SG, Lee SH, Kim J, et al. Beta-catenin gene alterations in a variety of so-called calcifying odontogenic cysts. APMIS 2008;116:206–11.10.1111/j.1600-0463.2008.00893.xSearch in Google Scholar

16. Hassanein AM, Glanz SM. Beta-catenin expression in benign and malignant pilomatrix neoplasms. Br J Dermatol 2004;150:511–6.10.1046/j.1365-2133.2004.05811.xSearch in Google Scholar

17. Burghaus S, Hölsken A, Buchfelder M, Fahlbusch R, Riederer BM, et al. A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas. Virchows Arch 2010;456:287–300.10.1007/s00428-009-0873-0Search in Google Scholar

18. Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, et al. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 2002;161:1997–2001.10.1016/S0002-9440(10)64477-XSearch in Google Scholar

19. Kato K, Nakatani Y, Kanno H, Inayama Y, Ijiri R, et al. Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma. J Pathol 2004;203:814–21.10.1002/path.1562Search in Google Scholar PubMed

20. Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, et al. Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol 2005;109:589–97.10.1007/s00401-005-1004-xSearch in Google Scholar PubMed

21. Larkin SJ, Ansorge O. Pathology and pathogenesis of craniopharyngiomas. Pituitary 2013;16:9–17.10.1007/s11102-012-0418-4Search in Google Scholar

22. Holsken A, Kreutzer J, Hofmann BM, Hans V, Oppel F, et al. Target gene activation of the Wnt signaling pathway in nuclear beta-catenin accumulating cells of adamantinomatous craniopharyngiomas. Brain Pathol 2009;19:357–64.10.1111/j.1750-3639.2008.00180.xSearch in Google Scholar

23. Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, et al. Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci USA 2011;108:11482–7.10.1073/pnas.1101553108Search in Google Scholar

24. Buslei R, Hölsken A, Hofmann B, Kreutzer J, Siebzehnrubl F, et al. Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas. Acta Neuropathol 2007;113:585–90.10.1007/s00401-006-0184-3Search in Google Scholar

25. Holsken A, Stache C, Schlaffer SM, Flitsch J, Fahlbusch R, et al. Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche? Pituitary 2014;17:546–56.10.1007/s11102-013-0543-8Search in Google Scholar

26. Andoniadou CL, Gaston-Massuet C, Reddy R, Schneider RP, Blasco MA, et al. Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma. Acta Neuropathol 2012;124:259–71.10.1007/s00401-012-0957-9Search in Google Scholar

27. Hofmann BM, Kreutzer J, Saeger W, Buchfelder M, Blümcke I, et al. Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach. Am J Surg Pathol 2006;30:1595–603.10.1097/01.pas.0000213328.64121.12Search in Google Scholar

28. Stache C, Hölsken A, Fahlbusch R, Flitsch J, Schlaffer SM, et al. Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth. Neuro Oncol 2014;16:256–64.10.1093/neuonc/not195Search in Google Scholar

29. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell 2012;149:1192–205.10.1016/j.cell.2012.05.012Search in Google Scholar

30. Huelsken J, Birchmeier W. New aspects of Wnt signaling pathways in higher vertebrates. Curr Opin Genet Dev 2001;11:547–53.10.1016/S0959-437X(00)00231-8Search in Google Scholar

31. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781–810.10.1146/annurev.cellbio.20.010403.113126Search in Google Scholar

32. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet 1993;9:317–21.10.1016/0168-9525(93)90250-LSearch in Google Scholar

33. Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, et al. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 1996;382:638–42.10.1038/382638a0Search in Google Scholar PubMed

34. Behrens J, Jerchow BA, Würtele M, Grimm J, Asbrand C, et al. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science 1998;280:596–9.10.1126/science.280.5363.596Search in Google Scholar PubMed

35. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, et al. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996;272:1023–6.10.1126/science.272.5264.1023Search in Google Scholar PubMed

36. Rubinfeld B, Souza B, Albert I, Müller O, Chamberlain SH, et al. Association of the APC gene product with beta-catenin. Science 1993;262:1731–4.10.1126/science.8259518Search in Google Scholar PubMed

37. Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, et al. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 2002;16:1066–76.10.1101/gad.230302Search in Google Scholar PubMed PubMed Central

38. Provost E, McCabe A, Stern J, Lizardi I, D’Aquila TG, et al. Functional correlates of mutation of the Asp32 and Gly34 residues of beta-catenin. Oncogene 2005;24:2667–76.10.1038/sj.onc.1208346Search in Google Scholar PubMed

39. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. Beta-Catenin is a target for the ubiquitin-proteasome pathway. EMBO J 1997;16:3797–804.10.1093/emboj/16.13.3797Search in Google Scholar PubMed PubMed Central

40. He TC, Bauer A, Stappert J, Kispert A, Kemler R. Identification of c-MYC as a target of the APC pathway. Science 1998;281: 1509–12.10.1126/science.281.5382.1509Search in Google Scholar PubMed

41. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999;398:422–6.10.1038/18884Search in Google Scholar PubMed

42. Jho EH, Zhang T, Domon C, Joo CK, Freund JN, et al. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 2002;22:1172–83.10.1128/MCB.22.4.1172-1183.2002Search in Google Scholar PubMed PubMed Central

43. Kim JS, Crooks H, Dracheva T, Nishanian TG, Singh B, et al. Oncogenic beta-catenin is required for bone morphogenetic protein 4 expression in human cancer cells. Cancer Res 2002;62:2744–8.Search in Google Scholar

44. Muller T, Bain G, Wang X, Papkoff J. Regulation of epithelial cell migration and tumor formation by beta-catenin signaling. Exp Cell Res 2002;280:119–33.10.1006/excr.2002.5630Search in Google Scholar PubMed

45. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 2004;303:1483–7.10.1126/science.1094291Search in Google Scholar PubMed PubMed Central

46. Chan EF, Gat U, McNiff JM, Fuchs E. A common human skin tumour is caused by activating mutations in beta-catenin. Nat Genet 1999;21:410–3.10.1038/7747Search in Google Scholar PubMed

47. Kajino Y, Yamaguchi A, Hashimoto N, Matsuura A, Sato N, et al. Beta-Catenin gene mutation in human hair follicle-related tumors. Pathol Int 2001;51:543–8.10.1046/j.1440-1827.2001.01231.xSearch in Google Scholar PubMed

48. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 1997;275:1787–90.10.1126/science.275.5307.1787Search in Google Scholar PubMed

49. Taniguchi K, Roberts LR, Aderca IN, Dong X, Qian C, et al. Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene 2002;21:4863–71.10.1038/sj.onc.1205591Search in Google Scholar PubMed

50. Andoniadou CL, Signore M, Sajedi E, Gaston-Massuet C, Kelberman D, et al. Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. Development 2007;134:1499–508.10.1242/dev.02829Search in Google Scholar PubMed PubMed Central

51. Jayakody SA, Andoniadou CL, Gaston-Massuet C, Signore M, Cariboni A, et al. SOX2 regulates the hypothalamic-pituitary axis at multiple levels. J Clin Invest 2012;122:3635–46.10.1172/JCI64311Search in Google Scholar PubMed PubMed Central

52. Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, et al. Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell 2013;13:433–45.10.1016/j.stem.2013.07.004Search in Google Scholar PubMed

53. Alison MR, Murphy G, Leedham S. Stem cells and cancer: a deadly mix. Cell Tissue Res 2008;331:109–24.10.1007/s00441-007-0510-7Search in Google Scholar PubMed

54. Clarke MF, Fuller M. Stem cells and cancer: two faces of eve. Cell 2006;124:1111–5.10.1016/j.cell.2006.03.011Search in Google Scholar PubMed

55. Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer 2012;12:133–43.10.1038/nrc3184Search in Google Scholar PubMed

56. Visvader JE, Lindeman GJ. Cancer stem cells: current status and evolving complexities. Cell Stem Cell 2012;10:717–28.10.1016/j.stem.2012.05.007Search in Google Scholar PubMed

57. Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009;457:603–7.10.1038/nature07589Search in Google Scholar PubMed PubMed Central

58. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009;457:608–11.10.1038/nature07602Search in Google Scholar PubMed

59. Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, et al. Non-cell-autonomous tumor suppression by p53. Cell 2013;153:449–60.10.1016/j.cell.2013.03.020Search in Google Scholar PubMed PubMed Central

60. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 2003;33:416–21.10.1038/ng1099Search in Google Scholar PubMed

61. Demehri S, Turkoz A, Kopan R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell 2009;16:55–66.10.1016/j.ccr.2009.05.016Search in Google Scholar PubMed PubMed Central

62. Kode A, Manavalan JS, Mosialou I, Bhagat G, Rathinam CV, et al. Leukaemogenesis induced by an activating beta-catenin mutation in osteoblasts. Nature 2014;506:240–4.10.1038/nature12883Search in Google Scholar

63. Caretti V, Sewing AC, Lagerweij T, Schellen P, Bugiani M, et al. Human pontine glioma cells can induce murine tumors. Acta Neuropathol 2014;127:897–909.10.1007/s00401-014-1272-4Search in Google Scholar

64. Deschene ER, Myung P, Rompolas P, Zito G, Sun TY, et al. Beta-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche. Science 2014;343:1353–6.10.1126/science.1248373Search in Google Scholar

65. Mendelsohn J. Blockade of receptors for growth factors: an anticancer therapy – the Fourth Annual Joseph H Burchenal American Association of Cancer Res Clinical Research Award Lecture. Clin Cancer Res 2000;6:747–53.Search in Google Scholar

66. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 2004;59(Suppl):21–6.10.1016/j.ijrobp.2003.11.041Search in Google Scholar

67. Holsken A, Gebhardt M, Buchfelder M, Fahlbusch R, Blümcke I, et al. EGFR signaling regulates tumor cell migration in craniopharyngiomas. Clin Cancer Res 2011;17:4367–77.10.1158/1078-0432.CCR-10-2811Search in Google Scholar

68. Lee CH, Hung HW, Hung PH, Shieh YS. Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer. Mol Cancer 2010;9:64.10.1186/1476-4598-9-64Search in Google Scholar

69. Lu Z, Ghosh S, Wang Z, Hunter T. Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell 2003;4:499–515.10.1016/S1535-6108(03)00304-0Search in Google Scholar

70. Ono M, Kuwano M. Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res 2006;12:7242–51.10.1158/1078-0432.CCR-06-0646Search in Google Scholar PubMed

71. Laurent-Puig P, Lievre A, Blons H. Mutations and response to epidermal growth factor receptor inhibitors. Clin Cancer Res 2009;15:1133–9.10.1158/1078-0432.CCR-08-0905Search in Google Scholar PubMed

72. Roskoski R Jr. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res 2014;79:34–74.10.1016/j.phrs.2013.11.002Search in Google Scholar PubMed

73. Herbst RS, Fukuoka M, Baselga J. Gefitinib – a novel targeted approach to treating cancer. Nat Rev Cancer 2004;4:956–65.10.1038/nrc1506Search in Google Scholar PubMed

74. Alvarez-Medina R, Le Dreau G, Ros M, Martí E. Hedgehog activation is required upstream of Wnt signalling to control neural progenitor proliferation. Development 2009;136:3301–9.10.1242/dev.041772Search in Google Scholar PubMed

75. Ingham PW, Placzek M. Orchestrating ontogenesis: variations on a theme by sonic hedgehog. Nat Rev Genet 2006;7:841–50.10.1038/nrg1969Search in Google Scholar PubMed

76. Shin K, Lee J, Guo N, Kim J, Lim A, et al. Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 2011;472:110–4.10.1038/nature09851Search in Google Scholar PubMed PubMed Central

77. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 2010;468:1095–9.10.1038/nature09587Search in Google Scholar PubMed PubMed Central

78. Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/–)p53(–/–) mice. Cancer Cell 2004;6:229–40.10.1016/j.ccr.2004.08.019Search in Google Scholar PubMed

79. Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, et al. A paracrine requirement for hedgehog signalling in cancer. Nature 2008;455:406–10.10.1038/nature07275Search in Google Scholar PubMed

80. Theunissen JW, de Sauvage FJ. Paracrine Hedgehog signaling in cancer. Cancer Res 2009;69:6007–10.10.1158/0008-5472.CAN-09-0756Search in Google Scholar PubMed

81. Musani V, Gorry P, Basta-Juzbasic A, Stipic T, Miklic P, et al. Mutation in exon 7 of PTCH deregulates SHH/PTCH/SMO signaling: possible linkage to WNT. Int J Mol Med 2006;17:755–9.10.3892/ijmm.17.5.755Search in Google Scholar

82. Bijlsma MF, Roelink H. Non-cell-autonomous signaling by Shh in tumors: challenges and opportunities for therapeutic targets. Expert Opin Ther Targets 2010;14:693–702.10.1517/14728222.2010.497488Search in Google Scholar PubMed PubMed Central

83. Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov 2006;5:1026–33.10.1038/nrd2086Search in Google Scholar PubMed

84. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009;361:1173–8.10.1056/NEJMoa0902903Search in Google Scholar PubMed PubMed Central

85. Stache C, Hölsken A, Schlaffer SM, Hess A, Metzler M, et al. Insights into the infiltrative behavior of adamantinomatous craniopharyngioma in a new xenotransplant mouse model. Brain Pathol 2014. doi: 10.1111/bpa.12148 [Epub ahead of print].10.1111/bpa.12148Search in Google Scholar PubMed PubMed Central

86. Larkin SJ, Preda V, Karavitaki N, Grossman A, Ansorge O. BRAF V600E mutations are characteristic for papillary craniopharyngioma and may coexist with CTNNB1-mutated adamantinomatous craniopharyngioma. Acta Neuropathol 2014;127:927–9.10.1007/s00401-014-1270-6Search in Google Scholar PubMed PubMed Central

Received: 2014-10-23
Accepted: 2014-11-4
Published Online: 2014-12-11
Published in Print: 2015-1-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Childhood Craniopharyngioma
  3. Selected papers from the 3rd International Multidisciplinary Postgraduate Course, April 24–27, 2014
  4. Childhood craniopharyngioma – current status and recent perspectives in diagnostics and treatment
  5. The importance of interdisciplinary communication with patients about complex, chronic illnesses: our experiences as parents of a child with a craniopharyngioma
  6. Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models
  7. Endocrine aspects and sequel in patients with craniopharyngioma
  8. Surgery for pediatric craniopharyngiomas: is less more?
  9. Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma
  10. Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience
  11. Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity
  12. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment
  13. Review article
  14. Association study of TAC3 and TACR3 gene polymorphisms with idiopathic precocious puberty in Chinese girls
  15. Images in pediatric endocrinology
  16. Intestinal invagination in diabetic ketoacidosis: case report
  17. Original articles
  18. Managing incidental findings and disclosure of results in a paediatric research cohort – the LIFE Child Study cohort
  19. The heterogeneity of hyperinsulinaemic hypoglycaemia in 19 patients with Beckwith-Wiedemann syndrome due to KvDMR1 hypomethylation
  20. Gender differences and age-related changes in body fat mass in Tibetan children and teenagers: an analysis by the bioelectrical impedance method
  21. A study of genes involved in adipocyte differentiation
  22. Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?
  23. The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance
  24. Growth failure associated with early neglect: pilot comparison of neglected US children and international adoptees
  25. Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions
  26. Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys
  27. Skin advanced glycation endproducts are elevated at onset of type 1 diabetes in youth
  28. Can optical coherence tomography predict early retinal microvascular pathology in type 1 diabetic adolescents without minimal diabetic retinopathy? A single-centre study
  29. Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin
  30. Influence of catch-up growth on abdominal fat distribution in very low birth weight children – cohort study
  31. Thyrotoxic, hypokalemic periodic paralysis (THPP) in adolescents
  32. Pulmonary function in children with type 1 diabetes mellitus
  33. Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification
  34. Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial
  35. Vitamin D-containing supplements for children between 1–3 years of age: Are they essential for bone health?
  36. Anti-Mullerian hormone levels in American girls by age and race/ethnicity
  37. The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III
  38. Thyroid disease in Chinese girls with Turner syndrome
  39. Patient reports
  40. Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report
  41. Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene
  42. Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance
  43. A case of pediatric ectopic thyroid in lateral lymph nodes
  44. Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature
  45. Needle detachment from the Sure-T® infusion set in two young children with diabetes mellitus (DM) treated with continuous subcutaneous insulin infusion (CSII) and unexplained hyperglycaemia
  46. Familial dysalbuminemic hyperthyroxinemia in a 4-year-old girl with hyperactivity, palpitations and advanced dental age: how gold standard assays may be misleading
https://doi.org/10.1515/jpem-2014-0442
Keywords for this article
beta-catenin; craniopharyngioma; EGFR; mouse models; pituitary; sonic hedgehog; stem cells; tumours

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Childhood Craniopharyngioma
  3. Selected papers from the 3rd International Multidisciplinary Postgraduate Course, April 24–27, 2014
  4. Childhood craniopharyngioma – current status and recent perspectives in diagnostics and treatment
  5. The importance of interdisciplinary communication with patients about complex, chronic illnesses: our experiences as parents of a child with a craniopharyngioma
  6. Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models
  7. Endocrine aspects and sequel in patients with craniopharyngioma
  8. Surgery for pediatric craniopharyngiomas: is less more?
  9. Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma
  10. Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience
  11. Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity
  12. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment
  13. Review article
  14. Association study of TAC3 and TACR3 gene polymorphisms with idiopathic precocious puberty in Chinese girls
  15. Images in pediatric endocrinology
  16. Intestinal invagination in diabetic ketoacidosis: case report
  17. Original articles
  18. Managing incidental findings and disclosure of results in a paediatric research cohort – the LIFE Child Study cohort
  19. The heterogeneity of hyperinsulinaemic hypoglycaemia in 19 patients with Beckwith-Wiedemann syndrome due to KvDMR1 hypomethylation
  20. Gender differences and age-related changes in body fat mass in Tibetan children and teenagers: an analysis by the bioelectrical impedance method
  21. A study of genes involved in adipocyte differentiation
  22. Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?
  23. The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance
  24. Growth failure associated with early neglect: pilot comparison of neglected US children and international adoptees
  25. Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions
  26. Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys
  27. Skin advanced glycation endproducts are elevated at onset of type 1 diabetes in youth
  28. Can optical coherence tomography predict early retinal microvascular pathology in type 1 diabetic adolescents without minimal diabetic retinopathy? A single-centre study
  29. Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin
  30. Influence of catch-up growth on abdominal fat distribution in very low birth weight children – cohort study
  31. Thyrotoxic, hypokalemic periodic paralysis (THPP) in adolescents
  32. Pulmonary function in children with type 1 diabetes mellitus
  33. Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification
  34. Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial
  35. Vitamin D-containing supplements for children between 1–3 years of age: Are they essential for bone health?
  36. Anti-Mullerian hormone levels in American girls by age and race/ethnicity
  37. The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III
  38. Thyroid disease in Chinese girls with Turner syndrome
  39. Patient reports
  40. Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report
  41. Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene
  42. Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance
  43. A case of pediatric ectopic thyroid in lateral lymph nodes
  44. Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature
  45. Needle detachment from the Sure-T® infusion set in two young children with diabetes mellitus (DM) treated with continuous subcutaneous insulin infusion (CSII) and unexplained hyperglycaemia
  46. Familial dysalbuminemic hyperthyroxinemia in a 4-year-old girl with hyperactivity, palpitations and advanced dental age: how gold standard assays may be misleading
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Winner of the OpenAthens UX Award 2026
Winner of the OpenAthens UX Award 2026
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 6.3.2026 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2014-0442/html
Scroll to top button