Skip to main content
SpringerLink
Log in

Searching for E-cadherin gene mutations in early onset diffuse gastric cancer and hereditary diffuse gastric cancer in Korean patients

  • Original Article
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

The impact of CDH1 gene mutations and large deletions on hereditary diffuse gastric cancer (HDGC) and early onset diffuse gastric cancer (EODGC) has not been determined in Asians. We investigated the mutation status of the CDH1 gene in 25 Korean EODGC patients younger than 50 years and 23 HDGC patients who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. We determined that 2 of 25 (8 %) EODGC patients had CDH1 germline mutations. One was a nonsense mutation (c.1003C>T, p.Arg335*, exon 7) in a 41-year-old female with no family history of cancer. The other was a missense mutation (c.715G>A, p.Gly239Arg, exon 6) in a 28-year-old male with no family history of cancer. One of 23 (4.3 %) HDGC patients had a CDH1 germline mutation (c.1003C>T). The patient’s brother and sister died of stomach cancer. The MLPA results revealed no deletion or duplication in any patient. More research is needed to determine additional genetic targets that trigger HDGC. More comprehensive methods such as next-generation sequencing might be a good approach that can be used to identify the genetic causes of pathogenetically unexplained disorders.

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.

Fig. 1

Similar content being viewed by others

References

  1. Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3(11):e442

    Article  PubMed  Google Scholar 

  2. Roviello F, Corso G, Pedrazzani C et al (2007) High incidence of familial gastric cancer in Tuscany, a region in Italy. Oncology 72(3–4):243–247

    Article  PubMed  Google Scholar 

  3. Bernini M, Barbi S, Roviello F et al (2006) Family history of gastric cancer: a correlation between epidemiologic findings and clinical data. Gastric Cancer 9(1):9–13

    Article  PubMed  Google Scholar 

  4. Carneiro F, Oliveira C, Suriano G, Seruca R (2008) Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer. J Clin Pathol 61(1):25–30

    Article  PubMed  CAS  Google Scholar 

  5. Fitzgerald RC, Hardwick R, Huntsman D et al (2010) Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 47(7):436–444

    Article  PubMed  CAS  Google Scholar 

  6. Caldas C, Carneiro F, Lynch HT et al (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36(12):873–880

    PubMed  CAS  Google Scholar 

  7. Koea JB, Karpeh MS, Brennan MF (2000) Gastric cancer in young patients: demographic, clinicopathological, and prognostic factors in 92 patients. Ann Surg Oncol 7(5):346–351

    Article  PubMed  CAS  Google Scholar 

  8. Corso G, Marrelli D, Pascale V, Vindigni C, Roviello F (2012) Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature. BMC Cancer 12:8

    Article  PubMed  CAS  Google Scholar 

  9. Umeyama K, Sowa M, Kamino K, Kato Y, Satake K (1982) Gastric carcinoma in young adults in Japan. Anticancer Res 2(5):283–286

    PubMed  CAS  Google Scholar 

  10. Ramos-De la Medina A, Salgado-Nesme N, Torres-Villalobos G, Medina-Franco H (2004) Clinicopathologic characteristics of gastric cancer in a young patient population. J Gastrointest Surg 8(3):240–244

    Article  PubMed  Google Scholar 

  11. Lim S, Lee HS, Kim HS, Kim YI, Kim WH (2003) Alteration of E-cadherin-mediated adhesion protein is common, but microsatellite instability is uncommon in young age gastric cancers. Histopathology 42(2):128–136

    Article  PubMed  CAS  Google Scholar 

  12. Corso G, Pedrazzani C, Pinheiro H et al (2011) E-cadherin genetic screening and clinico-pathologic characteristics of early onset gastric cancer. Eur J Cancer 47(4):631–639

    Article  PubMed  CAS  Google Scholar 

  13. Suriano G, Oliveira C, Ferreira P et al (2003) Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands. Hum Mol Genet 12(5):575–582

    Article  PubMed  CAS  Google Scholar 

  14. Kaurah P, Huntsman DG. Hereditary Diffuse Gastric Cancer. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. June 21, 2011 [cited 2012 Feb 23]; Available from http://www.ncbi.nlm.nih.gov/books/NBK1139

  15. Guilford P, Hopkins J, Harraway J et al (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392(6674):402–405

    Article  PubMed  CAS  Google Scholar 

  16. Yamada H, Shinmura K, Ito H, et al. (2011) Germline alterations in the CDH1 gene in familial gastric cancer in the Japanese population. Cancer Sci 102(10):1782–1788

    Google Scholar 

  17. Oliveira C, Senz J, Kaurah P et al (2009) Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 18(9):1545–1555

    Article  PubMed  CAS  Google Scholar 

  18. de Moura Gallo CV, Azevedo ESMG, de Moraes E, Olivier M, Hainaut P (2005) TP53 mutations as biomarkers for cancer epidemiology in Latin America: current knowledge and perspectives. Mutat Res 589(3):192–207

    Article  PubMed  Google Scholar 

  19. Kim IJ, Kang HC, Shin Y et al (2004) A TP53-truncating germline mutation (E287X) in a family with characteristics of both hereditary diffuse gastric cancer and Li-Fraumeni syndrome. J Hum Genet 49(11):591–595

    Article  PubMed  CAS  Google Scholar 

  20. Oliveira C, Ferreira P, Nabais S et al (2004) E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients. Eur J Cancer 40(12):1897–1903

    Article  PubMed  CAS  Google Scholar 

  21. Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49

    PubMed  CAS  Google Scholar 

  22. More H, Humar B, Weber W et al (2007) Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene. Hum Mutat 28(2):203

    Article  PubMed  CAS  Google Scholar 

  23. Kaurah P, MacMillan A, Boyd N et al (2007) Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297(21):2360–2372

    Article  PubMed  CAS  Google Scholar 

  24. Kim S, Ki CS, Kim KM, Lee MG, Bae JM, Kim JW (2011) Novel mechanism of a CDH1 splicing mutation in a Korean patient with signet ring cell carcinoma. BMB Rep 44(11):725–729

    Article  PubMed  CAS  Google Scholar 

  25. Brooks-Wilson AR, Kaurah P, Suriano G et al (2004) Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41(7):508–517

    Article  PubMed  CAS  Google Scholar 

  26. Yoon KA, Ku JL, Yang HK, Kim WH, Park SY, Park JG (1999) Germline mutations of E-cadherin gene in Korean familial gastric cancer patients. J Hum Genet 44(3):177–180

    Article  PubMed  CAS  Google Scholar 

  27. Kim HC, Wheeler JM, Kim JC et al (2000) The E-cadherin gene (CDH1) variants T340A and L599 V in gastric and colorectal cancer patients in Korea. Gut 47(2):262–267

    Article  PubMed  CAS  Google Scholar 

  28. Keller G, Vogelsang H, Becker I et al (2004) Germline mutations of the E-cadherin(CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients. J Med Genet 41(6):e89

    Article  PubMed  CAS  Google Scholar 

  29. Lee JH, Han SU, Cho H et al (2000) A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19(43):4947–4953

    Article  PubMed  CAS  Google Scholar 

  30. Kim IJ, Park JH, Kang HC et al (2003) A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer. J Med Genet 40(8):e97

    Article  PubMed  Google Scholar 

  31. Suriano G, Yew S, Ferreira P et al (2005) Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management. Clin Cancer Res 11(15):5401–5409

    Article  PubMed  CAS  Google Scholar 

  32. Jonsson BA, Bergh A, Stattin P, Emmanuelsson M, Gronberg H (2002) Germline mutations in E-cadherin do not explain association of hereditary prostate cancer, gastric cancer and breast cancer. Int J Cancer 98(6):838–843

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a faculty research grand of Gachon University, Gil Medical Center for 2010.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, South Korea

    Sollip Kim

  2. Department of Internal Medicine, Gil Medical Center, Gachon Graduate School of Medicine, Inchon, South Korea

    Jun-Won Chung

  3. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea

    Tae-Dong Jeong, Woochang Lee, Sail Chun & Won-Ki Min

  4. Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea

    Young-Soo Park

  5. Department of Gastroenterology, University of Ulsan College of Medicine and Asan Medical Centerr, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea

    Jeong Hoon Lee, Ji Yong Ahn, Do Hoon Kim, Kee Don Choi, Ho June Song, Gin Hyug Lee, Hwoon-Yong Jung & Jin-Ho Kim

Authors
  1. Sollip Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun-Won Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tae-Dong Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young-Soo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeong Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ji Yong Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Do Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kee Don Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Woochang Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ho June Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gin Hyug Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sail Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hwoon-Yong Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Won-Ki Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jin-Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Woochang Lee or Hwoon-Yong Jung.

Additional information

Sollip Kim and Jun-Won Chung contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, S., Chung, JW., Jeong, TD. et al. Searching for E-cadherin gene mutations in early onset diffuse gastric cancer and hereditary diffuse gastric cancer in Korean patients. Familial Cancer 12, 503–507 (2013). https://doi.org/10.1007/s10689-012-9595-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-012-9595-6

Keywords

Search

Navigation