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APC gene deletions in gastric adenocarcinomas in a Chinese population: a correlation with tumour progression

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Abstract

Introduction

The adenomatous polyposis coli (APC) gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It has been shown to be involved in genetic instability and to be down-regulated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in gastric cancers (GCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples.

Patients and materials

Case-matched tissues of GC and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in gastric malignancies.

Results

Our results showed that copy number deletions of APC were present in a relatively high percentage (25.9%, 34 out of 131) of gastric cancer samples. There was a correlation between APC deletion and tumor progression (p<0.01) as well as gene expression (p<0.05) in collected GC samples. On the other hand, mRNA levels of APC were also impaired in GC samples with unaltered copy numbers.

Conclusion

Sporadic GCs exhibit different mechanisms of APC regulation.

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References

  1. Munemitsu S, Souza B, Muller O et al (1994) The APC gene product associates with microtubules in vivo and promaotes their assembly in vitro. Cancer Res 54:3676–3681

    PubMed  CAS  Google Scholar 

  2. Henderson BR (2000) Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover. Nat Cell Biol 2:653–660

    Article  PubMed  CAS  Google Scholar 

  3. Neufeld KL, Nix DA, Bogerd H et al (2000) Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm. Proc Natl Acad Sci U S A 97:12085–12090

    Article  PubMed  CAS  Google Scholar 

  4. Wong MH, Hermiston ML, Syder AJ, Gordon JI (1996) Forced expression of the tumor suppressor adenomatosis polyposis coli protein induces disordered cell migration in the intestinal epithelium. Proc Natl Acad Sci U S A 93:9588–9593

    Article  PubMed  CAS  Google Scholar 

  5. Narayan S, Roy D (2003) Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer 2:41

    Article  PubMed  Google Scholar 

  6. Smith KJ, Levy DB, Maupin P et al (1994) Wildtype but not mutant APC associates with the microtubule cytoskeleton. Cancer Res 54:3672–3675

    PubMed  CAS  Google Scholar 

  7. Barth AI, Pollack AL, Altschuler Y et al (1997) NH2-terminal deletion of beta-catenin results in stable colocalization of mutant beta-catenin with adenomatous polyposis coli protein and altered MDCK cell adhesion. J Cell Biol 136:693–706

    Article  PubMed  CAS  Google Scholar 

  8. Goss KH, Groden J (2000) Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol 18:1967–1979

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Huang J, Zheng S, Jin S (1996) [APC mutation analysis in sporadic colorectal cancer]. Zhonghua Zhong Liu Za Zhi 18:415–418

    PubMed  Google Scholar 

  11. Ruiz-Ponte C, Vega A, Carracedo A, Barros F (2001) Mutation analysis of the adenomatous polyposis coli (APC) gene in northwest Spanish patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer. Hum Mutat 18:355

    Article  PubMed  CAS  Google Scholar 

  12. Jiao YF, Sugai T, Habano W et al (2006) Clinicopathological significance of loss of heterozygosity in intestinal- and solid-type gastric carcinomas: a comprehensive study using the crypt isolation technique. Mod Pathol 19:548–555

    Article  PubMed  CAS  Google Scholar 

  13. Gumbiner BM (1997) Carcinogenesis: a balance between beta-catenin and APC. Curr Biol 7: R443–446

    Article  PubMed  CAS  Google Scholar 

  14. McCartney BM, Nathke IS (2008) Cell regulation by the Apc protein Apc as master regulator of epithelia. Curr Opin Cell Biol 20:186–193

    Article  PubMed  CAS  Google Scholar 

  15. Fang Z, Xiong Y, Li J et al (2011) Detection of APC gene deletions in colorectal malignancies using quantitative PCR in a Chinese population. Pathol Oncol Res 17:657–661

    Article  PubMed  CAS  Google Scholar 

  16. Vauhkonen H, Vauhkonen M, Sipponen P, Knuutila S (2007) Oligonucleotide array comparative genomic hybridization refines the structure of 8p23.1, 17q12 and 20q13.2 amplifications in gastric carcinomas. Cytogenet Genome Res 119:39–45

    Article  PubMed  CAS  Google Scholar 

  17. Vauhkonen H, Vauhkonen M, Sajantila A et al (2006) DNA copy number aberrations in intestinal-type gastric cancer revealed by array-based comparative genomic hybridization. Cancer Genet Cytogenet 167:150–154

    Article  PubMed  CAS  Google Scholar 

  18. van Dekken H, Vissers K, Tilanus HW et al (2006) Genomic array and expression analysis of frequent high-level amplifications in adenocarcinomas of the gastro-esophageal junction. Cancer Genet Cytogenet 166:157–162

    Article  PubMed  Google Scholar 

  19. Tamura G, Ogasawara S, Nishizuka S et al (1996) Two distinct regions of deletion on the long arm of chromosome 5 in differentiated adenocarcinomas of the stomach. Cancer Res 56:612–615

    PubMed  CAS  Google Scholar 

  20. Achille A, Baron A, Zamboni G et al (1998) Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer. Br J Cancer 78: 1653–1660

    Article  PubMed  CAS  Google Scholar 

  21. Fang DC, Luo YH, Yang SM et al (2002) Mutation analysis of APC gene in gastric cancer with microsatellite instability. World J Gastroenterol 8: 787–791

    PubMed  CAS  Google Scholar 

  22. Yu B, Shao Y, Li P et al (2010) Copy number variations of the human histamine H4 receptor gene are associated with systemic lupus erythematosus. Br J Dermatol 163:935–940

    Article  PubMed  CAS  Google Scholar 

  23. Redon R, Ishikawa S, Fitch KR et al (2006) Global variation in copy number in the human genome. Nature 444:444–454

    Article  PubMed  CAS  Google Scholar 

  24. Sun XJ, Zheng ZH, Fu H et al (2003) [The I1307K mutation and protein expression of APC gene in gastric cancer]. Yi Chuan 25:253–357

    PubMed  CAS  Google Scholar 

  25. Rhyu MG, Park WS, Jung YJ et al (1994) Allelic deletions of MCC/APC and p53 are frequent late events in human gastric carcinogenesis. Gastroenterology 106:1584–1588

    PubMed  CAS  Google Scholar 

  26. Sanz-Ortega J, Sanz-Esponera J, Caldes T et al (1996) LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications. Pathol Res Pract 192:1206–1210

    CAS  Google Scholar 

  27. Tamura G, Maesawa C, Suzuki Y et al (1993) Primary gastric carcinoma cells frequently lose heterozygosity at the APC and MCC genetic loci. Jpn J Cancer Res 84:1015–1018

    Article  PubMed  CAS  Google Scholar 

  28. Dermitzakis ET, Stranger BE (2006) Genetic variation in human gene expression. Mamm Genome 17:503–508

    Article  PubMed  Google Scholar 

  29. Reymond A, Henrichsen CN, Harewood L, Merla G (2007) Side effects of genome structural changes. Curr Opin Genet Dev 17:381–386

    Article  PubMed  CAS  Google Scholar 

  30. Tamura G, Maesawa C, Suzuki Y et al (1994) Mutations of the APC gene occur during early stages of gastric adenoma development. Cancer Res 54:1149–1151

    PubMed  CAS  Google Scholar 

  31. Ostwald C, Linnebacher M, Weirich V, Prall F (2009) Chromosomally and microsatellite stable colorectal carcinomas without the CpG island methylator phenotype in a molecular classification. Int J Oncol 35:321–327

    PubMed  CAS  Google Scholar 

  32. Lee BB, Lee EJ, Jung EH et al (2009) Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res 15:6185–6191

    Article  PubMed  CAS  Google Scholar 

  33. Chen SP, Chiu SC, Wu CC et al (2009) The association of methylation in the promoter of APC and MGMT and the prognosis of Taiwanese CRC patients. Genet Test Mol Biomarkers 13:67–71

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jun Wan.

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These authors contributed equally to this manuscript.

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Fang, Z., Xiong, Y., Li, J. et al. APC gene deletions in gastric adenocarcinomas in a Chinese population: a correlation with tumour progression. Clin Transl Oncol 14, 60–65 (2012). https://doi.org/10.1007/s12094-012-0762-x

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  • DOI: https://doi.org/10.1007/s12094-012-0762-x

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