Skip to main content
SpringerLink
Log in

Brain metastases exhibit gross deletions of the APC gene

  • Original Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

Candidate genes involved in metastasis to the brain require investigation. In the present study, the adenomatous polyposis coli (APC) gene was analyzed in a set of human brain metastases. Gross deletions of the APC gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using the restriction fragment length polymorphism method performed by the use of MspI and RsaI genetic markers inside exon 15 and exon 11. Among 21 brain metastases analyzed, 58.8% of samples showed LOH of the APC gene. When assigning the genetic changes to a specific primary tumor type, 6 LOHs were found in metastases originated from lung and 4 LOHs in metastases from colon. The main effector of the wnt signaling, beta-catenin, was upregulated in 42.9% of cases and transferred to the nucleus in 28.6% of metastasis cases. Our findings suggest that genetic changes of the tumor suppressor gene APC, a component of the wnt pathway, represent a part of the brain metastasis genetic profile.

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

Fig. 1

Similar content being viewed by others

References

  1. Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. Hum Mol Genet 10:721–733

    Article  PubMed  CAS  Google Scholar 

  2. Pećina-Šlaus N, Nikuševa Martić T, Tomas D et al (2008) Meningiomas exhibit loss of heterozygosity of the APC gene. J Neuro-Oncol 87:63–70

    Article  Google Scholar 

  3. Pećina-Šlaus N, Majić Ž, Musani V et al (2010) Report on mutation in exon 15 of the APC gene in a case of brain metastasis. J Neuro-Oncol 97:143–148

    Article  Google Scholar 

  4. Aretz S, Uhlhaas S, Sun Y et al (2004) Familial adenomatous polyposis: aberrant splicing due to missense or silent mutations in the APC gene. Hum Mutat 24:370–380

    Article  PubMed  CAS  Google Scholar 

  5. Klaus A, Birchmeier W (2008) Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8:8387–8398

    Article  Google Scholar 

  6. Bos PD, Zhang XH, Nadal C et al (2009) Genes that mediate breast cancer metastasis to the brain. Nature (Lond) 459:1005–1009

    Article  CAS  Google Scholar 

  7. Lagerwaard FJ, Levendag PC, Nowak PJ et al (1999) Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 43:795–803

    Article  PubMed  CAS  Google Scholar 

  8. Gupta GP, Minn AJ, Kang Y et al (2005) Identifying site-specific metastasis genes and functions. Cold Spring Harbor Symp Quant Biol 70:149–158

    Article  PubMed  CAS  Google Scholar 

  9. Albini A, Mirisola V, Pfeffer U (2008) Metastasis signatures: genes regulating tumor–microenvironment interactions predict metastatic behavior. Cancer Metastasis Rev 27:75–83

    Article  PubMed  CAS  Google Scholar 

  10. Götz R (2008) Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression. Cancer Cell Int 8:7

    Article  PubMed  Google Scholar 

  11. Chang SC, Lin JK, Lin TC et al (2005) Loss of heterozygosity: an independent prognostic factor of colorectal cancer. World J Gastroenterol 11:778–784

    PubMed  CAS  Google Scholar 

  12. D’Amico D, Carbone DP, Johnson BE et al (1992) Polymorphic sites within the MCC and APC loci reveal very frequent loss of heterozygosity in human small cell lung cancer. Cancer Res 52:1996–1999

    PubMed  Google Scholar 

  13. Cooper CA, Bubb VJ, Smithson N et al (1996) Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of APC mutation. J Pathol 180:33–37

    Article  PubMed  CAS  Google Scholar 

  14. Mazieres J, He B, You L et al (2005) Wnt signaling in lung cancer. Cancer Lett 222:1–10

    Article  PubMed  CAS  Google Scholar 

  15. Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol (Berl) 114:97–109

    Article  Google Scholar 

  16. Kim S, Lee D (2009) Mining metastasis related genes by primary-secondary tumor comparisons from large-scale databases. BMC Bioinforma 10(suppl 3):S2. doi:10.1186/1471-2105-10-S3-S2

  17. Kienast Y, von Baumgarten L, Fuhrmann M et al (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nat Med 16:116–122

    Article  PubMed  CAS  Google Scholar 

  18. Nathoo N, Chahlavi A, Barnett GH (2005) Pathobiology of brain metastases. J Clin Pathol 58:237–242

    Article  PubMed  CAS  Google Scholar 

  19. Schouten LJ, Rutten J, Huveneers HAM et al (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer (Phila) 94:2698–2705

    Article  Google Scholar 

  20. Lea IA, Jackson MA, Li X et al (2007) Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns. Carcinogenesis (Oxf) 28:1851–1858

    Article  CAS  Google Scholar 

  21. Ohgaki H, Kros JM, Okamoto Y et al (2004) APC mutations are infrequent but present in human lung cancer. Cancer Lett 207:197–203

    Article  PubMed  CAS  Google Scholar 

  22. Ding L, Getz G, Wheeler DA et al (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature (Lond) 455:1069–1075

    Article  CAS  Google Scholar 

  23. Nikuševa Martić T, Beroš V, Pećina-Šlaus N et al (2007) Genetic changes of CDH1, APC and CTNNB1 found in human brain tumors. Pathol Res Pract 203:779–787

    Article  PubMed  Google Scholar 

  24. Navin N, Krasnitz A, Rodgers L et al (2010) Inferring tumor progression from genomic heterogeneity. Genome Res 20:68–80

    Article  PubMed  CAS  Google Scholar 

  25. Kitaewa MN, Grogan L, Williams JP et al (1997) Mutations in beta-catenin are uncommon in colorectal cancer occurring. Cancer Res 57:4478–4481

    Google Scholar 

Download references

Acknowledgments

This work was supported by grant 108-1081870-1905 from the Ministry of Science Sports and Education, Republic of Croatia.

Author information

Authors and Affiliations

  1. Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, 10000, Zagreb, Croatia

    Nives Pećina-Šlaus, Tamara Nikuševa Martić, Martina Zeljko & Sandra Bulat

  2. Department of Biology, School of Medicine, University of Zagreb, Šalata 3, 10000, Zagreb, Croatia

    Nives Pećina-Šlaus & Tamara Nikuševa Martić

Authors
  1. Nives Pećina-Šlaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamara Nikuševa Martić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martina Zeljko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandra Bulat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nives Pećina-Šlaus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pećina-Šlaus, N., Nikuševa Martić, T., Zeljko, M. et al. Brain metastases exhibit gross deletions of the APC gene. Brain Tumor Pathol 28, 223–228 (2011). https://doi.org/10.1007/s10014-011-0030-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-011-0030-8

Keywords

Search

Navigation