P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development

International Journal of Cancer

Volumn 124, Issue 2, 2009, Pages 339-345

  Van Veelen, Wendy ^a,c,d   Klompmaker, Rob ^a   Gloerich, Martijn ^a   Van Gasteren, Carola J R ^a   Kalkhoven, Eric ^a   Berger, Ruud ^a,b   Lips, Cornelis J M ^a   Medema, Rene H ^a   Höppener, Jo W M ^a,b   Acton, Dennis S ^a,d  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b Netherlands Metabolomics Center   (Netherlands)

^c ERASMUS MEDICAL CENTER   (Netherlands)

^d NONE   (Netherlands)

Author keywords

Medullary thyroid carcinoma; Multistep tumorigenesis; P18 INK4C; RET; Tumor suppressor gene

Indexed keywords

CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; CYCLIN DEPENDENT KINASE INHIBITOR 2C; PROTEIN P18; PROTEIN RET;

AMINO ACID SUBSTITUTION; ARTICLE; CANCER INHIBITION; CARCINOGENESIS; CELL CYCLE REGULATION; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; PHEOCHROMOCYTOMA; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; SOMATIC MUTATION; THYROID MEDULLARY CARCINOMA; TUMOR SUPPRESSOR GENE; AMINO ACID SEQUENCE; BIOLOGICAL MODEL; BIOSYNTHESIS; DISEASE COURSE; GENE EXPRESSION REGULATION; MEDULLARY CARCINOMA; METABOLISM; MOLECULAR GENETICS; MUTATION; NUCLEOTIDE SEQUENCE; PHYSIOLOGY; SEQUENCE HOMOLOGY; THYROID TUMOR; TUMOR CELL LINE;

AMINO ACID SEQUENCE; CARCINOMA, MEDULLARY; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE INHIBITOR P18; DISEASE PROGRESSION; DNA MUTATIONAL ANALYSIS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; HUMANS; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; MUTATION; PHEOCHROMOCYTOMA; SEQUENCE HOMOLOGY, AMINO ACID; THYROID NEOPLASMS;

EID: 58249093583     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.23977     Document Type: Article

References (50)

1. Sizemore GW, Health H, III, Carney JA. Multiple endocrine neoplasia type 2. Clin Endocrinol Metab 1980;9:299-315.
2. Machens A, Gimm O, Hinze R, Hoppner W, Boehm BO, Dralle H. Genotype-phenotype correlations in hereditary medullary thyroid carcinoma: oncological features and biochemical properties. J Clin Endocrinol Metab 2001;86:1104-9.
3. Mulligan LM, Marsh DJ, Robinson BG, Schuffenecker I, Zedenius J, Lips CJ, Gagel RF, Takai SI, Noll WW, Fink M, Raue F, Lacroix A, et al. Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium. J Intern Med 1995;238:343-6.
4. Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, Howe JR, Moley JF, Goodfellow P, Wells SA, Jr. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 1993;2:851-6.
5. Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, Ponder MA, Telenius H, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993;363:458-60.
6. Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE, Wells SA, Jr, Goodfellow PJ, Donis-Keller H. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci USA 1994;91:1579-83.
7. Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, Gardner E, Scheumann GF, Jackson CE, Tunnacliffe A, Ponder BAJ. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet 1994;3:237-41.
8. Hofstra RM, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y, Pasini B, Hoppener JW, van Amstel HK, Romeo G, Lips CJM, Buys CHCM. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 1994;367:375-6.
9. Eng C, Mulligan LM. Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung disease. Hum Mutat 1997;9:97-109.
10. Khosla S, Patel VM, Hay ID, Schaid DJ, Grant CS, van Heerden JA, Thibodeau SN. Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas. J Clin Invest 1991;87:1691-9.
11. 11.Mathew CG, Smith BA, Thorpe K, Wong Z, Royle NJ, Jeffreys AJ, Ponder BA. Deletion of genes on chromosome 1 in endocrine neoplasia. Nature 1987;328:524-6.
12. Mulligan LM, Gardner E, Smith BA, Mathew CG, Ponder BA. Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2. Genes Chromosomes Cancer 1993;6:166-77.
13. Edstrom Elder E, Nord B, Carling T, Juhlin C, Backdahl M, Hoog A, Larsson C. Loss of heterozygosity on the short arm of chromosome 1 in pheochromocytoma and abdominal paraganglioma. World J Surg 2002;26:965-71.
14. Marsh DJ, Theodosopoulos G, Martin-Schulte K, Richardson AL, Philips J, Roher HD, Delbridge L, Robinson BG. Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 2003;88:1866-72.
15. Opocher G, Schiavi F, Vettori A, Pampinella F, Vitiello L, Calderan A, Vianello B, Murgia A, Martella M, Taccaliti A, Mantero F, Mostacciuolo ML. Fine analysis of the short arm of chromosome 1 in sporadic and familial pheochromocytoma. Clin Endocrinol (Oxf) 2003; 59:707-15.
16. Yang KP, Nguyen CV, Castillo SG, Samaan NA. Deletion mapping on the distal third region of chromosome 1p in multiple endocrine neoplasia type IIA. Anticancer Res 1990;10:527-33.
17. Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 1995;9:1149-63.
18. Bartkova J, Thullberg M, Rajpert-De Meyts E, Skakkebaek NE, Bartek J. Cell cycle regulators in testicular cancer: loss of p18INK4C marks progression from carcinoma in situ to invasive germ cell tumours. Int J Cancer 2000;85:370-5.
19. Morishita A, Masaki T, Yoshiji H, Nakai S, Ogi T, Miyauchi Y, Yoshida S, Funaki T, Uchida N, Kita Y, Funakoshi F, Usuki H, et al. Reduced expression of cell cycle regulator p18(INK4C) in human hepatocellular carcinoma. Hepatology 2004;40:677-86.
20. Uziel T, Zindy F, Xie S, Lee Y, Forget A, Magdaleno S, Rehg JE, Calabrese C, Solecki D, Eberhart CG, Sherr SE, Plimmer S, et al. The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation. Genes Dev 2005;19: 2656-67.
21. Sanchez-Aguilera A, Delgado J, Camacho FI, Sanchez-Beato M, Sanchez L, Montalban C, Fresno MF, Martin C, Piris MA, Garcia JF. Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Stern- berg cells in Hodgkin lymphomas. Blood 2004; 103:2351-7.
22. Franklin DS, Godfrey VL, Lee H, Kovalev GI, Schoonhoven R, Chen-Kiang S, Su L, Xiong Y. CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. Genes Dev 1998;12:2899-911.
23. Franklin DS, Godfrey VL, O'Brien DA, Deng C, Xiong Y. Functional collaboration between different cyclin-dependent kinase inhibitors suppresses tumor growth with distinct tissue specificity. Mol Cell Biol 2000;20:6147-58.
24. van Veelen W, van Gasteren CJ, Acton DS, Franklin DS, Berger R, Lips CJ, Hoppener JW. Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development. Cancer Res 2008;68:1329-37.
25. Bai F, Pei XH, Godfrey VL, Xiong Y. Haploinsufficiency of p18(INK4c) sensitizes mice to carcinogen-induced tumorigenesis. Mol Cell Biol 2003;23:1269-77.
26. Bai F, Pei XH, Pandolfi PP, Xiong Y. p18 Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control. Mol Cell Biol 2006;26:4564-76.
27. Uziel T, Zindy F, Sherr CJ, Roussel MF. The CDK inhibitor p18Ink4c is a tumor suppressor in medulloblastoma. Cell Cycle 2006;5:363-5.
28. Venkataramani R, Swaminathan K, Marmorstein R. Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations. Nat Struct Biol 1998;5:74-81.
29. He J, Hoang-Xuan K, Marie Y, Leuraud P, Mokhtari K, Kujas M, Delattre JY, Sanson M. P18 tumor suppressor gene and progression of oligodendrogliomas to anaplasia. Neurology 2000;55:867-9.
30. Husemann K, Wolter M, Buschges R, Bostrom J, Sabel M, Reifenberger G. Identification of two distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1p32 in oligodendroglial tumors. J Neuropathol Exp Neurol 1999;58:1041-50.
31. Blais A, Labrie Y, Pouliot F, Lachance Y, Labrie C. Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer. Biochem BiophysResCommun 1998;247:146-53.
32. Bostrom J, Meyer-Puttlitz B, Wolter M, Blaschke B, Weber RG, Lichter P, Ichimura K, Collins VP, Reifenberger G. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. Am J Pathol 2001;159:661-9.
33. Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1998;1378:F115-F177.
34. Hatta Y, Spirin K, Tasaka T, Morosetti R, Said JW, Yamada Y, Tomo-naga M, Koeffler HP. Analysis of p18INK4C in adult T-cell leukaemia and non-Hodgkin's lymphoma. Br J Haematol 1997;99:665-7.
35. Miller CW, Aslo A, Campbell MJ, Kawamata N, Lampkin BC, Koeffler HP. Alterations of the p15, p16,and p18 genes in osteosarcoma. Cancer Genet Cytogenet 1996;86:136-42.
36. Huang L, Goodrow TL, Zhang SY, Klein-Szanto AJ, Chang H, Ruggeri BA. Deletion and mutation analyses of the P16/MTS-1 tumor suppressor gene in human ductal pancreatic cancer reveals a higher frequency of abnormalities in tumor-derived cell lines than in primary ductal adenocarcinomas. Cancer Res 1996;56:1137-41.
37. Piccinin S, Doglioni C, Maestro R, Vukosavljevic T, Gasparotto D, D'Orazi C, Boiocchi M. p16/CDKN2 and CDK4 gene mutations in sporadic melanomadevelopmentandprogression. IntJCancer1997;74:26-30.
38. Pollock PM, Pearson JV, Hayward NK. Compilation of somatic mutations of the CDKN2 gene in human cancers: non-random distribution of base substitutions. Genes Chromosomes Cancer 1996;15:77-88.
39. Li J, Byeon IJ, Ericson K, Poi MJ, O'Maille P, Selby T, Tsai MD. Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A. Biochemistry 1999;38:2930-40.
40. Li J, Poi MJ, Qin D, Selby TL, Byeon IJ, Tsai MD. Tumor suppressor INK4: quantitative structure-function analyses of p18INK4C as an inhibitor of cyclin-dependent kinase 4. Biochemistry 2000;39:649-57.
41. Noh SJ, Li Y, Xiong Y, Guan KL. Identification of functional elements of p18INK4C essential for binding and inhibition of cyclin-dependent kinase (CDK) 4 and CDK6. Cancer Res 1999;59:558-64.
42. Venkataramani RN, MacLachlan TK, Chai X, El-Deiry WS, Marmorstein R. Structure-based design of p18INK4c proteins with increased thermodynamic stability and cell cycle inhibitory activity. J Biol Chem 2002;277:48827-33.
43. Yarbrough WG, Buckmire RA, Bessho M, Liu ET. Biologic and biochemical analyses of p16(INK4a) mutations from primary tumors. J Natl Cancer Inst 1999;91:1569-74.
44. Lapointe J, Lachance Y, Labrie Y, Labrie C. A p18 mutant defective in CDK6 binding in human breast cancercells. Cancer Res 1996;56:4586-9.
45. Parry D, Peters G. Temperature-sensitive mutants of p16CDKN2 associated with familial melanoma. Mol Cell Biol 1996;16:3844-52.
46. Kawamata N, Miller CW, Koeffler HP. Molecular analysis of a family of cyclin-dependent kinase inhibitor genes (p15/MTS2/INK4b and p18/ INK4c) in non-small cell lung cancers. Mol Carcinog 1995;14: 263-8.
47. Kawamata N, Seriu T, Koeffler HP, Bartram CR. Molecular analysis of the cyclin-dependent kinase inhibitor family: p16(CDKN2/MTS1/INK4A), p18(INK4C) and p27(Kip1) genes in neuroblastomas. Cancer 1996;77:570-5.
48. Park DJ, Wilczynski SP, Pham EY, Miller CW, Koeffler HP. Molecular analysis of the INK4 family of genes in prostate carcinomas. J Urol 1997;157:1995-9.
49. Takeuchi S, Bartram CR, Seriu T, Miller CW, Tobler A, Janssen JW, Reiter A, Ludwig WD, Zimmermann M, Schwaller J, Lee E, Miyoshi I, et al. Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood. Blood 1995;86:755-60.
50. Joshi PP, Kulkarni MV, Yu BK, Smith KR, Norton DL, Veelen W, Hoppener JW, Franklin DS. Simultaneous downregulation of CDK inhibitors p18(Ink4c) and p27(Kip1) is required for MEN2A-RET- mediated mitogenesis. Oncogene 2007;26:554-70.