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  • Oncogenomics
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Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function

Oncogene volume 20, pages 5554–5561 (2001)Cite this article

Abstract

Mutations of PTEN, which encodes a protein-tyrosine and lipid phosphatase, are prevalent in a variety of human cancers. The human genome ‘draft’ sequence still lacks organization and much of the PTEN and adjacent loci remain undefined. The pufferfish, Fugu rubripes, by virtue of having a compact genome represents an excellent template for rapid vertebrate gene discovery. Sequencing of 56 kb from the Fugu pten (fpten) locus identified four complete genes and one partial gene homologous to human genes. Genes neighboring fpten include a PAPS synthase (fpapss2) differentially expressed between non-metastatic/metastatic human carcinoma cell lines, an inositol phosphatase (fminpp1) and an omega class glutathione-S-transferase (fgsto). We have determined the order of human BAC clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes oriented as are their Fugu orthologs. Although the human genes span 500 kb, the Fugu genes lie within only 22 kb due to the compressed intronic and intergenic regions that typify this genome. Interestingly, and providing striking evidence of regulatory element conservation between widely divergent vertebrate species, the compact 2.1 kb fpten promoter is active in human cells. Also, like hPTEN, fpten has a growth and tumor suppressor activity in human glioblastoma cells, demonstrating conservation of protein function.

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References

  • Ausabel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K . 1995 In Current Protocols in Molecular Biology Vol. 2 pp. 9.7.1–9.7.11 John Wiley & Sons, Inc., New York, NY

    Google Scholar 

  • Bostrom J, Cobbers JM, Wolter M, Tabatabai G, Weber RG, Lichter P, Collins VP, Reifenberger G . 1998 Canc. Res. 58: 29–33

  • Brenner S, Elgar G, Sandford R, Macrae A, Venkatesh B, Aparicio S . 1993 Nature 366: 265–268

  • Cantley LC, Neel BG . 1999 Proc. Natl. Acad. Sci. USA 96: 4240–4245

  • Chi H, Tiller GE, Dasouki MJ, Romano PR, Wang J, O'Keefe RJ, Puzas JE, Rosier RN, Reynolds PR . 1999 Genomics 56: 324–336

  • Chi H, Yang X, Kingsley PD, O'Keefe RJ, Puzas JE, Rosier RN, Shears SB, Reynolds PR . 2000 Mol. Cell. Biol. 20: 6496–6507

  • Craxton A, Caffrey JJ, Burkhart W, Safrany ST, Shears SB . 1997 Biochem. J. 328: 75–81

  • Dahia PM, Gimm O, Chi H, Marsh DJ, Reynolds PR, Eng C . 2000 J. Med. Genet. 37: 715–717

  • Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP . 1998 Nat. Genet. 19: 348–355

  • Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB, Pandolfi PP . 1999 Science 285: 2122–2125

  • Di Cristofano A, Pandolfi PP . 2000 Cell 100: 387–390

  • Feilotter HE, Nagai MA, Boag AH, Eng C, Mulligan LM . 1998 Oncogene 16: 1743–1748

  • Feilotter HE, Coulon V, McVeigh JL, Boag AH, Dorion-Bonnet F, Duboue B, Latham WC, Eng C, Mulligan LM, Longy M . 1999 Br. J. Canc. 79: 718–723

  • Franzon VL, Gibson MA, Hatzinikolas G, Woollatt E, Sutherland GR, Cleary EG . 1999 Int. J. Biochem. Cell Biol. 31: 613–626

  • Fujisawa H, Kurrer M, Reis RM, Yonekawa Y, Kleihues P, Ohgaki H . 1999 Am. J. Pathol. 155: 387–394

  • Furnari FB, Lin H, Huang H-JS, Cavenee WK . 1997 Proc. Natl. Acad. Sci. USA 94: 12479–12484

  • Georgescu M-M, Kirsch KH, Akagi T, Shishido T, Hanafusa H . 1999 Proc. Natl. Acad. Sci. USA 96: 10182–10187

  • Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA, Podkolodny NL, Kolchanov NA . 1998 Nuc. Acids Res. 26: 364–370

  • Huang H, Potter CJ, Tao W, Li D-M, Brogiolo W, Hafen E, Sun H, Xu T . 1999 Development 126: 5365–5372

  • Kurima K, Warman ML, Krishnan S, Domowicz M, Krueger Jr RC, Deyrup A, Schwartz NB . 1998 Proc. Natl. Acad. Sci. USA 95: 8681–8685

  • Kurima K, Singh B, Schwartz NB . 1999 J. Biol. Chem. 274: 33306–33312

  • Lee J-O, Yang H, Georgescu M-M, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP . 1999 Cell 99: 323–334

  • Li D-M, Sun H . 1997 Canc. Res. 57: 2124–2129

  • Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Milaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittman M, Tycko B, Hibshoosh H, Wigler MH, Parsons R . 1997a Science 275: 1943–1947

  • Li L, Ernsting BR, Wishart MJ, Lohse DL, Dixon JE . 1997b J. Biol. Chem. 272: 29403–29406

  • Liaw D, Marsh DJ, Li J, Dahia PLM, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R . 1997 Nat. Genet. 16: 64–67

  • Maehama T, Dixon JE . 1998 J. Biol. Chem. 273: 13375–13378

  • Marsh DJ, Dahia PLM, Zheng Z, Liaw D, Parsons R, Gorlin RJ, Eng C . 1997 Nat. Genet. 16: 333–334

  • Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham Jr JM, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C et al . 1999 Hum. Mol. Genet. 8: 1461–1472

  • Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP, Eng C . 2000 J. Natl. Canc. Inst. 92: 861–863

  • Myers MP, Pass I, Batty IH, Van der Kaay J, Stolarov JP, Hemmings BA, Wigler MH, Downes CP, Tonks NK . 1998 Proc. Natl. Acad. Sci. USA 95: 13513–13518

  • Nogimori K, Hughes PJ, Glennon MC, Hodgson ME, Putney Jr JW, Shears SB . 1991 J. Biol. Chem. 266: 16499–16506

  • Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM, Cordon-Cardo C, Catoretti G, Fisher PE, Parsons R . 1999 Proc. Natl. Acad. Sci. USA 96: 1563–1568

  • Reynolds SD, Johnston CJ, Leboy PS, O'Keefe RJ, Puzas JE, Rosier RN, Reynolds PR . 1996 Exp. Cell Res. 226: 197–207

  • Romano PR, Wang J, O'Keefe RJ, Puzas JE, Rosier RN, Reynolds PR . 1998 J. Cell Sci. 111: 803–813

  • Rouault JP, Kuwabara PE, Sinilnikova OM, Duret L, Thierry-Mieg D, Billaud M . 1999 Curr. Biol. 9: 329–332

  • Simpkins SB, Peiffer-Schneider S, Mutch DG, Gersell D, Goodfellow PJ . 1998 Gynecol. Oncol. 71: 391–395

  • Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW . 1998 Cell 95: 29–39

  • Steck PA, Pershouse MA, Jassar SA, Yung WKA, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DHF, Tavtigian SV . 1997 Nat. Genet. 15: 356–362

  • Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I, Ho A, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak TW . 1998 Curr. Biol. 8: 1169–1178

  • Thompson JD, Higgins DG, Gibson TJ . 1994 Nuc. Acids Res. 22: 4673–4680

  • ul Haque MF, King LM, Krakow D, Cantor RM, Rusiniak ME, Swank RT, Superti-Furga A, Haque S, Abbas H, Ahmad W, Ahmad M, Cohn DH . 1998 Nat. Genet. 20: 157–162

  • Vazquez F, Ramaswamy S, Nakamura N, Sellers WR . 2000 Mol. Cell. Biol. 20: 5010–5018

  • Venkatesh B, Gilligan P, Brenner S . 2000 FEBS Lett. 476: 3–7

  • Zheng XM, Wang Y, Pallen CJ . 1992 Nature 359: 336–339

  • Zhou MP, Gimm O, Hampel H, Niemann T, Walker MJ, Eng C . 2000 Am. J. Pathol. 157: 1123–1128

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Acknowledgements

We thank the UK-HGMP Resource Centre for providing the Fugu cosmids, and CH Ng and BH Tay for excellent technical assistance. This work was supported by the National Science and Technology Board of Singapore, Industry Canada, the Province of British Columbia, and the Medical Research Council of Canada.

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Authors and Affiliations

  1. Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore, 117609, Republic of Singapore

    Wei-Ping Yu, Catherine J Pallen, Alice Tay, Sydney Brenner, Y H Tan & Byrappa Venkatesh

  2. Center for Molecular Medicine and Therapeutics, British Columbia Research Institute for Children's and Women's Health, 950 West 28th Avenue, University of British Columbia, Vancouver, B.C. V5Z 4H4, Canada

    Frank R Jirik

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  1. Wei-Ping Yu
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  2. Catherine J Pallen
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Correspondence to Catherine J Pallen.

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Yu, WP., Pallen, C., Tay, A. et al. Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function. Oncogene 20, 5554–5561 (2001). https://doi.org/10.1038/sj.onc.1204679

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