Abstract
One of the most consistently deleted chromosomal regions in solid tumours is 11q23–q25, which consequently has been postulated to harbour one or more tumour suppressor loci. Despite large efforts to identify the responsible genes, the goal remains elusive, but as knowledge accumulates new candidates are emerging. The present study was undertaken in an attempt to assess the possible implication of four genes residing at 11q23–q24, in a population of early onset breast cancer (n=41). The coding sequence of PIG8, CHK1, LOH11CR2A and PPP2R1B were screened for mutations using the protein truncation test or single-strand conformational polymorphism, in combination with direct DNA sequencing. Varying proportions of alterations were detected, ranging from 6% in PPP2R1B to 39% in PIG8. Many of these changes were deletions, in some cases corresponding to complete exons, thus likely to represent splice variants, while others were presumed to arise from aberrant splicing, since they occurred at sites with resemblance to exon/intron borders. Considering only bona fide mutations, the highest alteration frequency (17%) was again found in PIG8. Most of these alterations were likely to have an adverse impact on the translated protein as they either altered the reading frame or affected phylogenetically conserved residues. Our data represent the first evidence of alterations in the PIG8 gene in human malignancies, a finding that substantiates its role as a potential tumour suppressor gene as suggested by its involvement in p53-induced apoptosis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Athma P, Rappaport R, Swift M . 1996 Cancer Genet. Cytogenet. 92: 130–134
Bebb DG, Yu Z, Chen J, Telatar M, Gelmon K, Phillips N, Gatti RA, Glickman BW . 1999 Br. J. Cancer 80: 1979–1981
Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA . 1999 Science 286: 2528–2531
Bertoni F, Codegoni AM, Furlan D, Tibiletti MG, Capella C, Broggini M . 1999 Genes Chromosomes Cancer 26: 176–180
Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, Rutgers EJ, Devilee P, Russell NS, van Leeuwen FE, van't Veer LJ . 2000 Am. J. Hum. Genet. 66: 494–500
Calin GA, di Iasio MG, Caprini E, Vorechovsky I, Natali PG, Sozzi G, Croce CM, Barbanti-Brodano G, Russo G, Negrini M . 2000 Oncogene 19: 1191–1195
Easton DF . 1994 Int. J. Radiat. Biol. 66: S177–S182
Evans MF, Koreth J, Bakkenist CJ, Herrington CS, McGee JO . 1998 Oncogene 16: 2557–2564
FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA . 1997 Nat. Genet. 15: 307–310
Gentile M, Bergman Jungeström M, Olsen KE, Söderkvist P, Wingren S . 1999a Eur. J. Cancer 35: 1202–1207
Gentile M, Olsen K, Dufmats M, Wingren S . 1999b Br. J. Cancer 80: 843–849
Gentile M, Wiman A, Thorstenson S, Loman N, Borg A, Wingren S . 2001 Int. J. Cancer 92: 208–213
Gu Z, Flemington C, Chittenden T, Zambetti GP . 2000a Mol. Cell. Biol. 20: 233–241
Gu Z, Gilbert DJ, Valentine VA, Jenkins NA, Copeland NG, Zambetti GP . 2000b Cytogenet. Cell Genet. 89: 230–233
Hampton GM, Mannermaa A, Winquist R, Alavaikko M, Blanco G, Taskinen PJ, Kiviniemi H, Newsham I, Cavenee WK, Evans GA . 1994 Cancer Res. 54: 4586–4589
Haruki N, Saito H, Tatematsu Y, Konishi H, Harano T, Masuda A, Osada H, Fujii Y, Takahashi T . 2000 Cancer Res. 60: 4689–4692
Hayashi K, Yandell DW . 1993 Hum. Mutat. 2: 338–346
Herbst RA, Gutzmer R, Matiaske F, Mommert S, Casper U, Kapp A, Weiss J . 1999 Int. J. Cancer 80: 205–209
Hui AB, Lo KW, Leung SF, Choi PH, Fong Y, Lee JC, Huang DP . 1996 Cancer Res. 56: 3225–3229
Izatt L, Greenman J, Hodgson S, Ellis D, Watts S, Scott G, Jacobs C, Liebmann R, Zvelebil MJ, Mathew C, Solomon E . 1999a Genes Chromosomes Cancer 26: 286–294
Izatt L, Vessey C, Hodgson SV, Solomon E . 1999b Eur. J. Hum. Genet. 7: 310–320
Janin N, Andrieu N, Ossian K, Lauge A, Croquette MF, Griscelli C, Debre M, Bressac-de-Paillerets B, Aurias A, Stoppa-Lyonnet D . 1999 Br. J. Cancer 80: 1042–1045
Kerangueven F, Eisinger F, Noguchi T, Allione F, Wargniez V, Eng C, Padberg G, Theillet C, Jacquemier J, Longy M, Sobol H, Birnbaum D . 1997 Oncogene 14: 339–347
Koreth J, Bakkenist CJ, McGee JO . 1997 Oncogene 14: 431–437
Laake K, Launonen V, Niederacher D, Gudlaugsdottir S, Seitz S, Rio P, Champeme MH, Bieche I, Birnbaum D, White G, Sztan M, Sever N, Plummer S, Osorio A, Broeks A, Huusko P, Spurr N, Borg A, Cleton-Jansen AM, van't Veer L, Benitez J, Casey G, Peterlin B, Olah E, Borresen-Dale AL, the Breast Cancer Somatic Genetic Consortium . 1999 Genes Chromosomes Cancer 25: 212–221
Laake K, Vu P, Andersen TI, Erikstein B, Karesen R, Lonning PE, Skovlund E, Borresen-Dale AL . 2000 Br. J. Cancer 83: 1650–1653
Lehar SM, Nacht M, Jacks T, Vater CA, Chittenden T, Guild BC . 1996 Oncogene 21: 1181–1187
Liu W, Qian C, Francke U . 1997 Nat. Genet. 16: 328–329
Monaco C, Negrini M, Sozzi G, Veronese ML, Vorechovsky I, Godwin AK, Croce CM . 1997 Genomics 46: 217–222
Murakami Y, Nobukuni T, Tamura K, Maruyama T, Sekiya T, Arai Y, Gomyou H, Tanigami A, Ohki M, Cabin D, Frischmeyer P, Hunt P, Reeves RH . 1998 Proc. Natl. Acad. Sci. USA 95: 8153–8158
Negrini M, Rasio D, Hampton GM, Sabbioni S, Rattan S, Carter SL, Rosenberg AL, Schwartz GF, Shiloh Y, Cavenee WK, CM Croce . 1995 Cancer Res. 55: 3003–3007
Olsen JH, Hahnemann JM, Borresen-Dale AL, Brondum-Nielsen K, Hammarstrom L, Kleinerman R, Kaariainen H, Lonnqvist T, Sankila R, Seersholm N, Tretli S, Yuen J, Boice Jr JD, Tucker M . 2001 J. Natl. Cancer Inst. 93: 121–127
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B . 1997 Nature 389: 300–305
Roest PA, Roberts RG, Sugino S, van Ommen GJ, den Dunnen JT . 1993 Hum. Mol. Genet. 2: 1719–1721
Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ . 1997 Science 277: 1497–1501
Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Simmons A, Clines G, Sartiel A, Gatti R, Chessa L, Sanal O, Lavin M, Miki T, Weissman S, Lovett M, Collin F, Shiloh Y . 1995a Science 268: 1749–1753
Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G . 1995b Hum. Mol. Genet. 4: 2025–2032
Siah SP, Quinn DM, Bennett GD, Casey G, Flower RL, Suthers G, Rudzki Z . 2000 Breast Cancer Res. Treat. 60: 135–142
Swift M, Morrell D, Massey RB, Chase CL . 1991 N. Engl. J. Med. 325: 1831–1836
Takagi Y, Futamura M, Yamaguchi K, Aoki S, Takahashi T, Saji S . 2000 Gut. 47: 268–271
Valentine CR . 1998 Mutat Res. 411: 87–117
Walter G, Mumby M . 1993 Biochim. Biophys. Acta 1155: 207–226
Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA . 1998 Science 282: 284–287
Wera S, Hemmings BA . 1995 Biochem. J. 311: 17–29
Vorechovsky I, Rasio D, Luo L, Monaco C, Hammarstrom L, Webster AD, Zaloudik J, Barbanti-Brodani G, James M, Russo G, et al . 1996 Cancer Res. 56: 2726–2732
Acknowledgements
This work was supported by grants from The Foundation of the National Board of Health and Welfare, The Regional Cancer Society of Östergötland, The Research Funds at the University Hospital of Linköping, Lions Research Foundation and The Research Council in the South-East of Sweden
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gentile, M., Ahnström, M., Schön, F. et al. Candidate tumour suppressor genes at 11q23–q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis. Oncogene 20, 7753–7760 (2001). https://doi.org/10.1038/sj.onc.1204993
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204993
