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Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma

Oncogene volume 24, pages 2684–2694 (2005)Cite this article

Abstract

Substantial genomic and functional evidence from primary tumors and cell lines indicates that a consistent region of distal chromosome 1p is deleted in a sizable proportion of human neuroblastomas, suggesting that this region contains one or more tumor suppressor genes. To determine systematically and precisely the location and extent of 1p deletion in neuroblastomas, we performed allelic loss studies of 737 primary neuroblastomas and genotype analysis of 46 neuroblastoma cell lines. Together, the results defined a single region within 1p36.3 that was consistently deleted in 25% of tumors and 87% of cell lines. Two neuroblastoma patients had constitutional deletions of distal 1p36 that overlapped the tumor-defined region. The tumor- and constitutionally-derived deletions together defined a smallest region of consistent deletion (SRD) between D1S2795 and D1S253. The 1p36.3 SRD was deleted in all but one of the 184 tumors with 1p deletion. Physical mapping and DNA sequencing determined that the SRD minimally spans an estimated 729 kb. Genomic content and sequence analysis of the SRD identified 15 characterized, nine uncharacterized, and six predicted genes in the region. The RNA expression profiles of 21 of the genes were investigated in a variety of normal tissues. The SHREW1 and KCNAB2 genes both had tissue-restricted expression patterns, including expression in the nervous system. In addition, a novel gene (CHD5) with strong homology to proteins involved in chromatin remodeling was expressed mainly in neural tissues. Together, these results suggest that one or more genes involved in neuroblastoma tumorigenesis or tumor progression are likely contained within this region.

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References

  • Abel F, Sjoberg RM, Ejeskar K, Krona C and Martinsson T . (2002). Br. J. Cancer, 86, 596–604.

  • Altschul SF, Gish W, Miller W, Myers EW and Lipman DJ . (1990). J. Mol. Biol., 215, 403–410.

  • Amler LC, Corvi R, Praml C, Savelyeva L, Le Paslier D and Schwab M . (1995). Oncogene, 10, 1095–1101.

  • Bader SA, Fasching C, Brodeur GM and Stanbridge EJ . (1991). Cell Growth Differ., 2, 245–255.

  • Barker PE, Savelyeva L and Schwab M . (1993). Oncogene, 8, 3353–3358.

  • Bauer A, Savelyeva L, Claas A, Praml C, Berthold F and Schwab M . (2001). Genes Chromosomes Cancer, 31, 228–239.

  • Bentley DR, Deloukas P, Dunham A, French L, Gregory SG, Humphray SJ, Mungall AJ, Ross MT, Carter NP, Dunham I, Scott CE, Ashcroft KJ, Atkinson AL, Aubin K, Beare DM, Bethel G, Brady N, Brook JC, Burford DC, Burrill WD, Burrows C, Butler AP, Carder C, Catanese JJ, Clee CM, Clegg SM, Cobley V, Coffey AJ, Cole CG, Collins JE, Conquer JS, Cooper RA, Culley KM, Dawson E, Dearden FL, Durbin RM, de Jong PJ, Dhami PD, Earthrowl ME, Edwards CA, Evans RS, Gillson CJ, Ghori J, Green L, Gwilliam R, Halls KS, Hammond S, Harper GL, Heathcott RW, Holden JL, Holloway E, Hopkins BL, Howard PJ, Howell GR, Huckle EJ, Hughes J, Hunt PJ, Hunt SE, Izmajlowicz M, Jones CA, Joseph SS, Laird G, Langford CF, Lehvaslaiho MH, Leversha MA, McCann OT, McDonald LM, McDowall J, Maslen GL, Mistry D, Moschonas NK, Neocleous V, Pearson DM, Phillips KJ, Porter KM, Prathalingam SR, Ramsey YH, Ranby SA, Rice CM, Rogers J, Rogers LJ, Sarafidou T, Scott DJ, Sharp GJ, Shaw-Smith CJ, Smink LJ, Soderlund C, Sotheran EC, Steingruber HE, Sulston JE, Taylor A, Taylor RG, Thorpe AA, Tinsley E, Warry GL, Whittaker A, Whittaker P, Williams SH, Wilmer TE, Wooster R and Wright CL . (2001). Nature, 409, 942–943.

  • Bharti S, Handrow-Metzmacher H, Zickenheiner S, Zeitvogel A, Baumann R and Starzinski-Powitz A . (2004). Mol. Biol. Cell, 15, 397–406.

  • Biegel JA, White PS, Marshall HN, Fujimori M, Zackai EH, Scher CD, Brodeur GM and Emanuel BS . (1993). Am. J. Hum. Genet., 52, 176–182.

  • Birney E, Andrews TD, Bevan P, Caccamo M, Chen Y, Clarke L, Coates G, Cuff J, Curwen V, Cutts T, Down T, Eyras E, Fernandez-Suarez XM, Gane P, Gibbins B, Gilbert J, Hammond M, Hotz HR, Iyer V, Jekosch K, Kahari A, Kasprzyk A, Keefe D, Keenan S, Lehvaslaiho H, McVicker G, Melsopp C, Meidl P, Mongin E, Pettett R, Potter S, Proctor G, Rae M, Searle S, Slater G, Smedley D, Smith J, Spooner W, Stabenau A, Stalker J, Storey R, Ureta-Vidal A, Woodwark KC, Cameron G, Durbin R, Cox A, Hubbard T and Clamp M . (2004). Genome Res., 14, 925–928.

  • Brodeur GM . (2003). Nat. Rev. Cancer, 3, 203–216.

  • Brodeur GM, Sekhon GS and Goldstein MN . (1977). Cancer, 40, 2256–2263.

  • Burge C and Karlin S . (1997). J. Mol. Biol., 268, 78–94.

  • Caron H, Spieker N, Godfried M, Veenstra M, van Sluis P, de Kraker J, Voute P and Versteeg R . (2001). Genes Chromosomes Cancer, 30, 168–174.

  • Casciano I, Marchi JV, Muresu R, Volpi EV, Rozzo C, Opdenakker G and Romani M . (1996). Oncogene, 12, 2101–2108.

  • Cerignoli F, Guo X, Cardinali B, Rinaldi C, Casaletto J, Frati L, Screpanti I, Gudas LJ, Gulino A, Thiele CJ and Giannini G . (2002). Cancer Res., 62, 1196–1204.

  • De Toledo M, Coulon V, Schmidt S, Fort P and Blangy A . (2001). Oncogene, 20, 7307–7317.

  • Dracopoli NC, Stanger BZ, Ito CY, Call KM, Lincoln SE, Lander ES and Housman DE . (1988). Am. J. Hum. Genet., 43, 462–470.

  • Eggert A, Brodeur GM and Ikegaki N . (2000). Biotechniques, 28, 681–682, 686, 688–691.

  • Ejeskar K, Abel F, Sjoberg R, Backstrom J, Kogner P and Martinsson T . (2000). Cytogenet Cell Genet., 89, 62–66.

  • Fong CT, Dracopoli NC, White PS, Merrill PT, Griffith RC, Housman DE and Brodeur GM . (1989). Proc. Natl. Acad. Sci. USA, 86, 3753–3757.

  • Godfried MB, Veenstra M, Valent A, Sluis P, Voute PA, Versteeg R and Caron HN . (2002). Eur. J. Cancer, 38, 1513–1519.

  • Grenet J, Valentine V, Kitson J, Li H, Farrow SN and Kidd VJ . (1998). Genomics, 49, 385–393.

  • Heilstedt HA, Ballif BC, Howard LA, Lewis RA, Stal S, Kashork CD, Bacino CA, Shapira SK and Shaffer LG . (2003). Am. J. Hum. Genet., 72, 1200–1212.

  • Heilstedt HA, Burgess DL, Anderson AE, Chedrawi A, Tharp B, Lee O, Kashork CD, Starkey DE, Wu YQ, Noebels JL, Shaffer LG and Shapira SK . (2001). Epilepsia, 42, 1103–1111.

  • Hogarty MD, Liu X, Guo C, Thompson PM, Weiss MJ, White PS, Sulman EP, Brodeur GM and Maris JM . (2000). Med. Pediatr. Oncol., 35, 512–515.

  • Hogarty MD, Winter CL, Liu X, Guo C, White PS, Look AT, Brodeur GM and Maris JM . (2002). Cancer Res., 62, 6481–6484.

  • Huang S, Lichtenauer UD, Pack S, Wang C, Kim AC, Lutchman M, Koch CA, Torres-Cruz J, Huang SC, Benz Jr EJ, Christiansen H, Dockhorn-Dworniczak B, Poremba C, Vortmeyer AO, Chishti AH and Zhuang Z . (2001). Eur. J. Clin. Invest., 31, 907–914.

  • Ishibashi M, Sasai Y, Nakanishi S and Kageyama R . (1993). Eur. J. Biochem., 215, 645–652.

  • Janoueix-Lerosey I, Novikov E, Monteiro M, Gruel N, Schleiermacher G, Loriod B, Nguyen C and Delattre O . (2004). Oncogene, 23, 5912–5922.

  • Jensen SJ, Sulman EP, Maris JM, Matise TC, Vojta PJ, Barrett JC, Brodeur GM and White PS . (1997). Genomics, 42, 126–136.

  • Judson H, van Roy N, Strain L, Vandesompele J, Van Gele M, Speleman F and Bonthron DT . (2000). Hum. Genet., 106, 406–413.

  • Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu YT, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ, Weber RJ, Haussler D and Kent WJ . (2003). Nucleic Acids Res., 31, 51–54.

  • Katoh M and Katoh M . (2003). Int. J. Oncol., 23, 1219–1224.

  • Katoh M and Katoh M . (2004). Int. J. Oncol., 25, 529–534.

  • Krona C, Ejeskar K, Abel F, Kogner P, Bjelke J, Bjork E, Sjoberg RM and Martinsson T . (2003). Oncogene, 22, 2343–2351.

  • Letovsky SI, Cottingham RW, Porter CJ and Li PW . (1998). Nucleic Acids Res., 26, 94–99.

  • Maris JM, Guo C, Blake D, White PS, Hogarty MD, Thompson PM, Rajalingam V, Gerbing R, Stram DO, Matthay KK, Seeger RC and Brodeur GM . (2001). Med. Pediatr. Oncol., 36, 32–36.

  • Maris JM, Jensen J, Sulman EP, Beltinger CP, Allen C, Biegel JA, Brodeur GM and White PS . (1997). Eur. J. Cancer, 33, 1991–1996.

  • Maris JM, Kyemba SM, Rebbeck TR, White PS, Sulman EP, Jensen SJ, Allen C, Biegel JA, Yanofsky RA, Feldman GL and Brodeur GM . (1996). Cancer Res., 56, 3421–3425.

  • Maris JM, Weiss MJ, Guo C, Gerbing RB, Stram DO, White PS, Hogarty MD, Sulman EP, Thompson PM, Lukens JN, Matthay KK, Seeger RC and Brodeur GM . (2000). J. Clin. Oncol., 18, 1888–1899.

  • Maris JM, White PS, Beltinger CP, Sulman EP, Castleberry RP, Shuster JJ, Look AT and Brodeur GM . (1995). Cancer Res., 55, 4664–4669.

  • Martinsson T, Sjoberg RM, Hallstensson K, Nordling M, Hedborg F and Kogner P . (1997). Eur. J. Cancer, 33, 1997–2001.

  • Mathysen D, Van Roy N, Van Hul W, Laureys G, Ambros P, Speleman F and Wuyts W . (2004). Eur. J. Cancer, 40, 1255–1261.

  • McCormack K, Connor JX, Zhou L, Ho LL, Ganetzky B, Chiu SY and Messing A . (2002). J. Biol. Chem., 277, 13219–13228.

  • Mollet G, Salomon R, Gribouval O, Silbermann F, Bacq D, Landthaler G, Milford D, Nayir A, Rizzoni G, Antignac C and Saunier S . (2002). Nat. Genet., 32, 300–305.

  • Mora J, Cheung NK, Kushner BH, LaQuaglia MP, Kramer K, Fazzari M, Heller G, Chen L and Gerald WL . (2000). J. Mol. Diagn., 2, 37–46.

  • Murphy K, Raj T, Winters RS and White PS . (2004). Bioinformatics, 20, 588–590.

  • Nakatani K, Nishioka J, Itakura T, Nakanishi Y, Horinouchi J, Abe Y, Wada H and Nobori T . (2004). Int. J. Oncol., 24, 1407–1412.

  • Nishimura M, Isaka F, Ishibashi M, Tomita K, Tsuda H, Nakanishi S and Kageyama R . (1998). Genomics, 49, 69–75.

  • Ohira M, Kageyama H, Mihara M, Furuta S, Machida T, Shishikura T, Takayasu H, Islam A, Nakamura Y, Takahashi M, Tomioka N, Sakiyama S, Kaneko Y, Toyoda A, Hattori M, Sakaki Y, Ohki M, Horii A, Soeda E, Inazawa J, Seki N, Kuma H, Nozawa I and Nakagawara A . (2000). Oncogene, 19, 4302–4307.

  • Satge D, Moore SW, Stiller CA, Niggli FK, Pritchard-Jones K, Bown N, Benard J and Plantaz D . (2003). Cancer Genet. Cytogenet., 147, 89–98.

  • Savelyeva L, Corvi R and Schwab M . (1994). Am. J. Hum. Genet., 55, 334–340.

  • Schleiermacher G, Peter M, Michon J, Hugot JP, Vielh P, Zucker JM, Magdelenat H, Thomas G and Delattre O . (1994). Genes Chromosomes Cancer, 10, 275–281.

  • Shapira SK, McCaskill C, Northrup H, Spikes AS, Elder FF, Sutton VR, Korenberg JR, Greenberg F and Shaffer LG . (1997). Am. J. Hum. Genet., 61, 642–650.

  • Spieker N, Beitsma M, Van Sluis P, Chan A, Caron H and Versteeg R . (2001). Genes Chromosomes Cancer, 31, 172–181.

  • Takayama H, Suzuki T, Mugishima H, Fujisawa T, Ookuni M, Schwab M, Gehring M, Nakamura Y, Sugimura T, Terada M and Yokota J . (1992). Oncogene, 7, 1185–1189.

  • Takeda O, Homma C, Maseki N, Sakurai M, Kanda N, Schwab M, Nakamura Y and Kaneko Y . (1994). Genes Chromosomes Cancer, 10, 30–39.

  • Thompson PM, Gotoh T, Kok M, White PS and Brodeur GM . (2003). Oncogene, 22, 1002–1011.

  • Thompson PM, Maris JM, Hogarty MD, Seeger RC, Reynolds CP, Brodeur GM and White PS . (2001). Cancer Res., 61, 679–686.

  • van der Drift P, Chan A, Laureys G, van Roy N, Sickmann G, den Dunnen J, Westerveld A, Speleman F and Versteeg R . (1995). Genes Chromosomes Cancer, 14, 35–42.

  • Van Roy N, Vandesompele J, Berx G, Staes K, Van Gele M, De Smet E, De Paepe A, Laureys G, van der Drift P, Versteeg R, Van Roy F and Speleman F . (2002). Genes Chromosomes Cancer, 35, 113–120.

  • Wheeler DL, Church DM, Edgar R, Federhen S, Helmberg W, Madden TL, Pontius JU, Schuler GD, Schriml LM, Sequeira E, Suzek TO, Tatusova TA and Wagner L . (2004). Nucleic Acids Res., 32 Database issue, D35–D40.

  • White PS, Maris JM, Beltinger C, Sulman E, Marshall HN, Fujimori M, Kaufman BA, Biegel JA, Allen C, Hilliard C, Valentine MB, Look AT, Enomoto H, Sakiyama S and Brodeur GM . (1995). Proc. Natl. Acad. Sci. USA, 92, 5520–5524.

  • White PS, Maris JM, Sulman EP, Jensen SJ, Kyemba SM, Beltinger CP, Allen C, Kramer DL, Biegel JA and Brodeur GM . (1997). Eur. J. Cancer, 33, 1957–1961.

  • White PS, Sulman EP, Porter CJ and Matise TC . (1999). Genome Res., 9, 978–988.

  • White PS, Thompson PM, Seifried BA, Sulman EP, Jensen SJ, Guo C, Maris JM, Hogarty MD, Allen C, Biegel JA, Matise TC, Gregory SG, Reynolds CP and Brodeur GM . (2001). Med. Pediatr. Oncol., 36, 37–41.

  • White PS and Versteeg R . (2000). Neuroblastoma. Brodeur GM, Sawada T, Tsuchida Y and Voute PA (eds). Elsevier: Amsterdam, pp 57–74.

    Google Scholar 

  • Woodage T, Basrai MA, Baxevanis AD, Hieter P and Collins FS . (1997). Proc. Natl. Acad. Sci. USA, 94, 11472–11477.

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Acknowledgements

This work was supported in part by NIH Grant CA039771 (GMB), CA087847 (JMM), the Abramson Family Cancer Research Institute, and the Audrey E Evans Endowed Chair (GMB). We gratefully acknowledge H Marshall, C Beltinger, E Sulman, M Fujimori, B Kaufman, S Jensen, and C Guo for previously reported LOH data used in the current study, and the Children's Oncology Group for access to patient material.

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Authors and Affiliations

  1. Division of Oncology, The Children's Hospital of Philadelphia, 3516 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Peter S White, Patricia M Thompson, Takahiro Gotoh, Erin R Okawa, Jun Igarashi, Marleen Kok, Cynthia Winter, Michael D Hogarty, John M Maris & Garrett M Brodeur

  2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Peter S White, Michael D Hogarty, John M Maris & Garrett M Brodeur

  3. Center for Human Genetics, Duke University School of Medicine, Durham, NC, 27710, USA

    Simon G Gregory

  4. Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    John M Maris

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  1. Peter S White
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White, P., Thompson, P., Gotoh, T. et al. Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene 24, 2684–2694 (2005). https://doi.org/10.1038/sj.onc.1208306

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