Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

Genetics of adenocarcinomas of the small intestine: frequent deletions at chromosome 18q and mutations of the SMAD4 gene

Oncogene volume 21, pages 158–164 (2002)Cite this article

Abstract

The small intestinal mucosa makes up about 90% of the total surface of the gastrointestinal tract. However, adenocarcinomas arise rarely in this location. To elucidate genetic alterations underlying tumour development in the small intestine we investigated 17 sporadic adenocarcinomas. By comparative genomic hybridization recurrent gains of chromosomal material were found at chromosomes 7, 8, 13q, and 20 (5/17, each), while non-random losses were seen at 8p, 17p (4/17, each), and 18 (8/17 cases). Deletions at 5q, the location of the APC tumour suppressor gene, were seen in three cases. Microsatellite analysis with markers on chromosomal arms 1p, 5q, 8p, 17p, 18q, 19p, and 22q revealed a microsatellite instable phenotype in two cases and a high frequency of loss at 18q21-q22 (80%). Given the high incidence of 18q21-q22 deletions, we performed sequencing analysis of SMAD4, a downstream component of the TGFβ-pathway, located at 18q21. Four tumours displayed mutations in highly conserved domains of the gene indicating disruption of TGFβ-signalling. Our data reveal complex genetic alterations in sporadic small intestinal carcinomas. However, most tumours share deletions of 18q21-q22, which frequently target SMAD4. This indicates that disruption of TGFβ-signalling plays a critical role in small intestinal tumorigenesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Arai M, Shimizu S, Imai Y, Nakatsuru Y, Oda H, Oohara T, Ishikawa T . 1997 Int. J. Cancer 70: 390–395

  • Arber N, Shapira I, Ratan J, Stern B, Hibshoosh H, Moshkowitz M, Gammon M, Fabian I, Halpern Z . 2000 Gastroenterology 118: 1045–1050

  • Bläker H, Hofmann WJ, Rieker RJ, Penzel R, Graf M, Otto HF . 1999 Genes Chromosom. Cancer 25: 399–402

  • DeAngelis PM, Clausen OP, Schjolberg A, Stokke T . 1999 Br. J. Cancer 80: 526–535

  • Emi M, Fujiwara Y, Nakajima T, Tsuchiya E, Tsuda H, Hirohashi S, Maeda Y, Tsuruta K, Miyaki M, Nakamura Y . 1992 Cancer Res. 52: 5368–5372

  • Houlston R, Bevan S, Williams A, Young J, Dunlop M, Rozen P, Eng C, Markie D, Woodford-Richens K, Rodriguez-Bigas MA, Leggett B, Neale K, Phillips R, Sheridan E, Hodgson S, Iwama T, Eccles D, Bodmer W, Tomlinson I . 1998 Hum. Mol. Genet. 7: 1907–1912

  • Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, Stone EM, Aaltonen LA . 1998 Science 280: 1086–1088

  • Isola J, DeVries S, Chu L, Siavash G, Waldman F . 1994 Am. J. Pathol. 145: 1301–1308

  • Jones JB, Kern SE . 2000 Nucleic Acids Res. 28: 2363–2368

  • Kim H, Jen J, Vogelstein B, Hamilton SR . 1994 Am. J. Pathol. 145: 148–156

  • Lightdale CJ, Hornsby-Lewis L . 1994 Bockus Gastroenterology Haubrich WS, Schaffner F, Berg JE (eds) W.B. Saunders Company: Philadelphia, London, Toronto, Montreal, Sydney, Tokyo pp. 1274–1290

    Google Scholar 

  • Lennard-Jones JE, Morson BC, Richie JK . 1977 Gastroenterology 73: 1280–1289

  • Lerebours F, Olschwang S, Thuille B, Schmitz A, Fouchet P, Laurent-Puig P, Boman F, Flejou JF, Monges G, Paraf F, Bedossa P, Sabourin JC, Salmon RJ, Parc R, Thomas G . 1999 Genes Chromosom. Cancer 25: 147–153

  • Logan RF, Rifkind EA, Turner ID, Ferguson A . 1989 Gastroenterology 97: 265–271

  • Mahlamaki EH, Hoglund M, Gerunova L, Karhu R, Dawiskiba S, Andren-Sandberg A, Kallioniemi OP, Johansson B . 1997 Genes Chromosom. Cancer 20: 383–391

  • Messerini L, Vitelli F, de Vitis LR, Mori S, Calzolari A, Palmirotta R, Calabro A, Papi L . 1997 J. Pathol. 182: 380–384

  • Ming S-C, Goldman H (eds) . 1992 Pathology of the gastrointestinal tract W.B. Saunders Company: Philadelphia, London, Toronto, Montreal, Sydney, Tokyo pp. 816–846

    Google Scholar 

  • Moore PS, Rigaud G, Baron A, Scarpa A . 2000 Hum. Mutat. 15: 485–486

  • Moser AR, Pitot HC, Dove WF . 1990 Science 247: 322–324

  • Moskaluk CA, Hruban RH, Schutte M, Lietman AS, Smyrk T, Fusari L, Fusaro R, Lynch J, Yeo CJ, Jackson E, Lynch HAT, Kern SE . 1997 Diagn. Mol. Pathol. 6: 85–90

  • Murata M, Iwao K, Miyoshi Y, Nagasawa Y, Ohta T, Shibata K, Oda K, Wada H, Tominaga S, Matsuda Y, Ohsawa M, Nakamura Y, Shimano T . 2000 Am. J. Gastroenterol. 95: 1576–1580

  • Negri E, Bosetti C, La Vecchia C, Fioretti F, Conti E, Franceschi S . 1999 Int. J. Cancer 82: 171–174

  • Neugut AI, Jacobsen JS, Suh S, Mukherjee R, Arber N . 1998 Cancer Epidemiol. Biomarker Prev. 7: 243–251

  • Park JG, Vasen HF, Park KJ, Peltomaki P, Ponz de Leon M, Rodriguez-Bigas MA, Lubinski J, Beck NE, Bisgaard ML, Miyaki M, Wijnen JT, Baba S, Lynch HAT . 1999 Dis. Colon Rectum 42: 710–715

  • Pohl C, Hombach A, Kruis W . 2000 Hepatogastroenterology 47: 57–70

  • Rashid A, Hamilton SR . 1997 Gastroenterology 113: 127–135

  • Roth S, Sistonen P, Salovaara R, Hemminki A, Loukola A, Johansson M, Avizienyte E, Cleary KA, Lynch P, Amos CI, Kristo P, Mecklin JP, Kellokumpu I, Jarvinen H, Aaltonen LA . 1999 Genes Chromosomes Cancer 26: 54–61

  • Sakakura C, Mori T, Sakabe T, Ariyama Y, Shinomiya T, Date K, Hagiwara A, Yamaguchi T, Takahashi T, Nakamura Y, Abe T, Inazawa J . 1999 Genes Chromosom. Cancer 24: 299–305

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

  • Shi Y, Hata A, Lo RS, Massague J, Pavletich NP . 1997 Nature 388: 87–93

  • Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK . 1989 Lancet 2: 783–785

  • Sutter T, Arber N, Moss S, Findling RI, Neugut AI, Weinstein IB, Holt PR . 1996 Dig. Dis. Sci. 41: 115–118

  • Tarapore P, Fukasawa K . 2000 Cancer Invest. 18: 148–155

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

  • Thibodeau SN, French AJ, Cunningham JM, Tester D, Burgart LJ, Roche PC, McDonnell SK, Schaid D, Vockley CW, Michels VV, Farr GH, O'Connell MJ . 1998 Cancer Res. 58: 1713–1718

  • Vasen HF, Watson P, Mecklin JP, Lynch HAT . 1999 Gastroenterology 116: 1453–1456

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

  • Whitelaw SC, Murday VA, Tomlinson IP, Thomas HJ, Cottrell S, Ginsberg A, Bukofzer S, Hodgson SV, Skudowitz RB, Jass JR, Talbot IC, Northover JM, Bodmer WF, Solomon E . 1997 Gastroenterology 112: 327–334

  • Xu X, Brodie SG, Yang X, Im YH, Parks WT, Chen L, Zhou YX, Weinstein M, Kim SJ, Deng CX . 2000 Oncogene 19: 1868–1874

  • Yustein AS, Harper JC, Petroni GR, Cummings OW, Moskaluk CA, Powell SM . 1999 Cancer Res. 59: 1437–1441

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg, 69120, Germany

    Hendrik Bläker, Axel von Herbay, Roland Penzel, Stefanie Groß & Herwart F Otto

Authors
  1. Hendrik Bläker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Axel von Herbay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roland Penzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefanie Groß
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Herwart F Otto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hendrik Bläker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bläker, H., von Herbay, A., Penzel, R. et al. Genetics of adenocarcinomas of the small intestine: frequent deletions at chromosome 18q and mutations of the SMAD4 gene. Oncogene 21, 158–164 (2002). https://doi.org/10.1038/sj.onc.1205041

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205041

Keywords

This article is cited by

Search

Advanced search

Quick links