Skip to main content
SpringerLink
Log in

Limiting the location of putative human prostate cancer tumor suppressor genes on chromosome 18q

  • Original Paper
  • Published:
Oncogene Submit manuscript

Abstract

We studied loss of heterozygosity (LOH) on the long arm of human chromosome 18 in prostate cancer to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the pathological grade and stage of the cancer. Of 48 specimens analysed 17 (35.4%) lost at least one allele on chromosome 18q. All the specimens with allelic losses lost at least one allele within chromosomal region 18q21. Allelic losses picked at D18S51 (19%) and D18S858 (17%). A 0.58 cM DNA segment that includes the D18S858 locus and is flanked by the microsatellite loci D18S41 and D18S381, was lost in eight (47%) of 17 specimens with allelic losses. This segment was designated as a LOH cluster region 1 (LCR 1). Although Smad2 resides within LCR 1, it was not mutated in any of the six prostate cell lines (five prostate cancer cell lines and one immortalized prostate epithelial cell line) analysed, suggesting that it is not a candidate TSG in prostate cancer. A second LCR at 18q21, LCR 2, includes the D18S51 locus and is flanked by the D18S1109 and D18S68 loci, which are separated by 7.64 cM. LCR 2 was lost in six (35%) of the 17 specimens with chromosome 18q losses. These results suggest that chromosome 18q21 may harbor two candidate prostate cancer TSGs. The candidate TSGs DCC and Smad4 are located centromeric to the LCRs. No alleles were lost within or in close proximity to these genes, suggesting that they are not targets for inactivation by allelic losses in prostate cancer. Although there was no obvious correlation between chromosome 18q LOH and the pathological grade or stage, three (37.5%) of eight low-grade cancers and nine (32.1%) of 28 organ-confined cancers lost alleles at 18q21, suggesting that allelic losses are relatively early events in the development of invasive prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Alexandrow MG, Moses HL . 1995 Cancer Res. 55: 1452–1457

  • Bergerheim US, Kunimi K, Collins VP, Ekman P . 1991 Genes Chromosomes Cancer. 3: 215–220

  • Bova GS, Carter BS, Bussemakers MJG, Emi M, Fujiwara Y, Kiprianou N, Jacobs SC, Robinson JC, Epstein JI, Walsh PC, Isaacs WB . 1993 Cancer Res. 53: 3869–3871

  • Brewster SF, Gingell JC, Browne S, Brown KW . 1994 Br. J. Cancer 70: 697–700

  • Brooks JD, Bova GS, Ewing CM, Piantadosi S, Carter BS, Robinson JC, Epstein JI, Isaacs WB . 1996 Cancer Res. 56: 3814–3822

  • Cairns P, Okami K, King P, Bonacum J, Ahrendt S, Wu L, Mao L, Jen J, Sidransky D . 1997 Cancer Res. 57: 5356–5359

  • Carter BS, Ewing CM, Ward WS, Treiger BF, Aalders TW, Schalken JA, Epstein JI, Isaacs WB . 1990 Proc. Natl. Acad. Sci. USA 87: 8751–8755

  • Chenevix-Trench G, Leary J, Kerr J, Michel J, Kefford R, Hurst T, Parson PG. Friedlander M, Khoo SK . 1992 Oncogene 7: 1059–1065

  • Cho KR, Oliner JD, Simons JW, Hedrick L, Fearon ER, Preisinger AC, Hedge P, Sikernian GA, Vogelstein B . 1994 Genomics 19: 525–531

  • Cliby W, Ritland S, Hartmann L, Dodson M, Hailing KC, Keeney G, Podrats KC, Jenkins RB . 1993 Cancer Res. 53: 2393–2398

  • Collins A, Frezal J, Teague J, Morton NE . 1996 Proc. Natl. Acad. Sci. USA 93: 14771–14775

  • Cooney KA, Wetzel JC, Merajver SD, Macoska JA, Singleton TP, Wojno KJ . 1996 Cancer Res. 56: 1142–1145

  • Cropp CS, Lidereau R, Campbell G, Champene MH, Callahan R . 1990 Proc. Natl. Acad. Sci. USA 87: 7737–7741

  • Crundwell MC, Chughtai S, Knowles M, Takle L, Luscombe M, Neoptolemos JP, Morton DG, Phillips SMA . 1996 Int. J. Cancer 69: 295–300

  • Cunningham JM, Shan A, Wick MJ, McDonnell SK, Schaid DJ, Tester DJ, Qian J, Takahashi S, Jenkins RB, Bostwick DG, Thibodeau SN . 1996 Cancer Res. 56: 4475–4482

  • Degeorges A, Hoffschir F, Cussenot O, Gauville C, Le Duc A, Dutrillaux B, Calvo F . 1995 Int. J. Cancer 62: 724–731

  • Devilee P, van Vliet M, Kuipers-Dijkshoorn N, Pearson PL, Cornelisse CJ . 1991 Oncogene 6: 311–315

  • Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, Lathrop M, Gyapay G, Morissette J, Weissenbach JA . 1996 Nature 380: 152–154

  • Eppert K, Scherer SW, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S, Andrulis IL, Thomsen GH, Wrana JL, Attisano L . 1996 Cell 86: 543–552

  • Fearon ER, Cho KR, Nigro JM, Kern SE, Simons LW, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW, Vogelstein B . 1990 Science 247: 49–56

  • Fleming ID, Cooper JS, Henson DE, Huntter RVP, Kennedy BJ, Murphy GP, O'Sullivan B, Sobin LH, Yarbro JW (eds) . 1997 AJCC cancer staging manual fifth edition Lippincott-Raven: Philadelphia

    Google Scholar 

  • Gao X, Horm KV, Grignon D, Sakr W, Chen YQ . 1993 Cancer Res. 53: 2723–2727

  • Gao X, Zacharek A, Salkowski A, Grignon DJ, Sakr W, Porter AT, Horm KV . 1995 Cancer Res. 55: 1002–1005

  • Gleason D . 1977 Urologic Pathology: The prostate. Tannenbaum M (ed) Lea & Febiger: Philadelphia pp. 171–197

  • Goggins M, Shekher M, Turnacioglu K, Yeo CJ, Hruban RH, Kern SE . 1998 Cancer Res. 58: 5329–5332

  • Hahn SA, Bartsch, Schroers A, Galehdari H, Becker M, Ramaswamy A, Schwarte-Waldhoff I, Maschek H, Schmiegel W . 1998 Cancer Res. 58: 1124–1126

  • Hahn SA, Schutte M, Hoque ATMS, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE . 1996 Science 271: 350–353

  • Hahn SA, Seumour AB, Hoque MS, Schutte M, da Costa LT, Redston MS, Caldas C, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kem SE . 1995 Cancer Res. 55: 4670–4675

  • Hedrick L, Cho KR, Fearon ER, Wit TC, Kinzler KW, Vogelstein B . 1994 Genes Dev. 8: 1174–1183

  • Huang Y, Boynton RF, Blount PL, Silverstein RI, Yin Y, Tong Y, McDaniel TK, Newkirk C, Resau JH, Sridhara R, Reid BJ, Meltzer S . 1992 Cancer Res. 52: 6525–6530

  • Ittmann M . 1996 Cancer Res. 56: 2143–2147

  • Jenkins R, Takahashi S, DeLacey K, Bergstralh E, Lieber M . 1998 Genes Chromosomes Cancer 21: 131–143

  • Kagan J, Stein J, Babaian RJ, Joe YS, Pisters LL, Glassman AB, von Eschenbach AC, Troncoso P . 1995 Oncogene 11: 2121–2126

  • Kim SK, Fan Y, Papadimitrakopoulou V, Clayman G, Hittelman WN, Hong WK, Lotan R, Mao L . 1996 Cancer Res. 56: 2519–2521

  • Kong XT, Choi SH, Inoue A, Xu F, Chen T, Takita J, Yokota J, Bessho F, Yanagisawa M, Hanada R, Yamamoto K, Hayashi Y . 1997 Cancer Res. 57: 3772–3778

  • Kunimi K, Bergerheim US, Larsson IL, Ekman P, Collins VP . 1991 Genomics 11: 530–536

  • Latil A, Baron JC, Cussenot O, Fournier G, Soussi T, Boccon-Gibod L, Le Duc A, Rouesse J, Lidereau R . 1994 Genes Chromosomes Cancer 11: 119–125

  • Latil A, Pesche S, Valeri A, Fournier G, Cussenot O, Lidereau R . 1999 Prostate 40: 225–231

  • Li C, Larsson C, Futreal A, Lancaster J, Phelan C, Aspenblad U, Sundelin B, Liu Y, Ekman P, Auer G, Bergerheim US . 1998 Oncogene 16: 481–487

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

  • MacGrogan D, Levy A, Bostwick D, Wagner M, Wells D, Bookstein R . 1994 Genes Chromosomes Cancer 10: 151–159

  • MacGrogan D, Pegram M, Slamon D, Bookstein R . 1997 Oncogene 15: 1111–1114

  • Macoska JA, Trybus TM, Benson PD, Sakr WA, Grignon DJ, Wojno KD, Pietruk T, Powell IJ . 1995 Cancer Res. 55: 5390–5395

  • Melamed J, Einhorn JM, Ittmann MM . 1997 Clin. Cancer Res. 3: 1867–1872

  • Mottaz AE, Markwalder R, Fey MF, Klima I, Merz VW, Thalmann GN, Ball RK, Studer UE . 1997 Prostate 31: 209–215

  • Nagatake M, Takagi Y, Osada H, Uchida K, Mitsudorni T, Saji S, Shimokata K, Takahashi T, Takahashi T . 1996 Cancer Res. 56: 2718–2720

  • Navone NM, Troncoso P, Pisters LL, Goodrow TL, Palmer JL, Nichols WW, Von Eschenbach AC, Conti CJ . 1993 J. Natl. Cancer Inst. 85: 1657–1659

  • Raff T, van der Giet M, Endemann D, Wiederholt T, Paul M . 1997 Biotechniques 23: 456–460

  • Reale MA, Hu G, Zafar AL, Getzenberg RH, Levine SM, Fearon ER . 1994 Cancer Res. 54: 4493–4501

  • Riggins GJ, Thiagalingarn S, Rozenblurn E, Weinstein CL, Kern SE, Hamilton SR, Willson JKV, Markowitz SD, Kinzler KW, Vogelstein B . 1996 Nat. Genet. 13: 347–349

  • Salem CE, Tomasic NA, Elmajian DA, Esrig D, Nichols PW, Taylor CR, Skinner DG, Roy-Burman P, Lieskovsky G, Cote RJ . 1997 J. Urology 158: 510–514

  • Schutte M, Hruban RH, Hedrick L, Cho KR, Nadasdy GM, Weinstein CL, Bova GS, Isaacs WB, Cairns P, Nawroz H, Sidransky D, Casero Jr RA, Meltzer PS, Hahn SA, Kern SE . 1996 Cancer Res. 56: 2527–2530

  • Shibagaki L, Shimada Y, Wagata T, lkenaga M, Imamura M,, Ishigaki K . 1994 Cancer Res. 54: 2995–3000

  • Shiseki M, Kohno T, Nishikawa R, Sameshima Y, Mizoguchi H,, Yokot J . 1994 Cancer Res. 54: 5643–5648

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

  • Suzuki H, Emi M, Komiya A, Fujiwara Y, Yatani R, Nakamura Y, Shimazaki J . 1995 Genes Chromosomes Cancer 13: 168–174

  • Takita J, Hayashi Y, Kohno T, Shiseki M, Yamaguchi N, Hanada R, Yamamoto K, Yokota J . 1995 Oncogene 11: 1829–1834

  • Teng DH, Hu R, Lin H, Davis T, Iliev D, Frye C, Swedlund B, Hansen KL, Vinson VL, Gumpper KL, Ellis L, El-Naggar A, Frazier M, Jasser S, Langford LA, Lee J, Mills GB, Pershouse MA, Pollack RE, Tornos C, Troncoso P, Yung WK, Fujii G, Berson A, Steck PA, et al. 1997 Cancer Res. 57: 5221–5225

  • Thiagalingam S, Lengauer C, Leach FS, Schutte M, Hahn SA, Overhauser J, Willson JKV, Markowitz S, Hamilton SR, Kern SE, Kinzier KW, Vogelstein B . 1996 Nat. Genet. 13: 343–346

  • Trapman J, Sleddens HF, van der Weiden MM, Dinjens WN, Konig JJ, Schroder FH, Faber PW, Bosman FT . 1994 Cancer Res. 54: 6061–6064

  • Uchida K, Nagatake M, Osada H, Yatabe Y, Kondo M, Mitsudomi T, Masuda A, Takahashi T, Takahashi T . 1996 Cancer Res. 56: 5583–5585

  • Uchino S, Tusda H, Noguchi M, Yokota J, Terada M, Saito T, Kofayashi M, Sugimura T, Hirohashi S . 1992 Cancer Res. 52: 3099–3102

  • Ueda T, Komiya A, Emi M, Suzuki H, Shiraishi T, Yatani R, Masai M, Yasuda K, Ito H . 1997 Genes Chromosomes Cancer 20: 140–147

  • Visakorpi T, Kallioniemi AH, Syvanen AC, Hyytinen ER, Karhu R, Tammela T, Isola, JJ, Kallioniemi OP . 1995 Cancer Res. 55: 342–347

  • Vogelstein B, Fearon E, Kern S, Hamilton S, Preisinger A, Nakamura Y, White R, Smits AM, Bos JL . 1988 N. Eng. J. Med. 319: 525–532

  • Weinberg RA . 1991 Science 254: 1138–1146

  • Yin Z, Spitz MR, Babaian RJ, Strom SS, Trocoso P, Kagan J . 1999 Oncogene 18: 7576–7583

  • Zar JH . 1991 Biostatistical analysis Prentice Hall: Englewood Cliffs, NJ

    Google Scholar 

  • Zenklusen JC, Thompson JC, Troncoso P, Kagan J, Conti CJ . 1994 Cancer Res. 54: 6370–6373

  • Zhang Y, Feng XH, Wu RY, Derynck R . 1996 Nature 383: 168–172

Download references

Acknowledgements

This study was supported by NCI grant CA68578-05(J Kagan and MR Spitz) and by The University of Texas M.D. Anderson Cancer Center Physician Referral Service Award (J Kagan).

Author information

Authors and Affiliations

  1. Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, 77030-4095, Texas, TX, USA

    Zhengnan Yin, Patricia Troncoso, Jimmy J Caudell, Jonathan D Stein & Jacob Kagan

  2. Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030-4095, Texas, TX, USA

    Richard J Babaian

  3. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030-4095, Texas, TX, USA

    Sara S Strom & Margaret R Spitz

Authors
  1. Zhengnan Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J Babaian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patricia Troncoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara S Strom
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margaret R Spitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jimmy J Caudell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jonathan D Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jacob Kagan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yin, Z., Babaian, R., Troncoso, P. et al. Limiting the location of putative human prostate cancer tumor suppressor genes on chromosome 18q. Oncogene 20, 2273–2280 (2001). https://doi.org/10.1038/sj.onc.1204310

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204310

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation