Skip to main content
SpringerLink
Log in
Book cover

Spotlight on Familial and Hereditary Gastric Cancer pp 35–49Cite as

E-Cadherin Germline Mutations

  • Chapter
  • First Online:

Abstract

Hereditary Diffuse Gastric Cancer is the only gastric cancer syndrome with a proven inherited defect. So far, a single gene has been found altered in this context – CDH1 – the E-cadherin encoding gene. Other E-cadherin-associated hereditary or inheritable disorders have been identified, encompassing Hereditary Diffuse Gastric Cancer families with or without cleft-lip/palate involvement, lobular breast cancer families, and early onset diffuse gastric cancers.

To date, 123 probands harboring 93 different CDH1 germline mutations have been described in these settings.

In this chapter, a summary of pathogenic and non-pathogenic CDH1 germline mutations identified to date will be described.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

CL/P:

Cleft Palate

DGC:

Diffuse Gastric Cancer

EODGC:

Early-Onset Diffuse Gastric Cancer

HDGC:

Hereditary Diffuse Gastric Cancer

IGC:

Intestinal Gastric Cancer

IGCLC:

International Gastric Cancer Linkage Consortium

LBC:

Lobular Breast Cancer

LOH:

Loss Of Heterozygosity

References

  • Bacani JT, Soares M, Zwingerman R, di Nicola N, Senz J, Riddell R, Huntsman DG, Gallinger S (2006) CDH1/E-cadherin germline mutations in early-onset gastric cancer. J Med Genet 43:867–872. doi:10.1136/jmg.2006.043133

    Article  PubMed  CAS  Google Scholar 

  • Barber ME, Save V, Carneiro F, Dwerryhouse S, Lao-Sirieix P, Hardwick RH, Caldas C, Fitzgerald RC (2008) Histopathological and molecular analysis of gastrectomy specimens from hereditary diffuse gastric cancer patients has implications for endoscopic surveillance of individuals at risk. J Pathol 216:286–294. doi:10.1002/path.2415

    Article  PubMed  CAS  Google Scholar 

  • Berx G, Cleton-Jansen AM, Nollet F, de Leeuw WJ, van de Vijver M, Cornelisse C, van Roy F (1995) E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J 14:6107–6115

    PubMed  CAS  Google Scholar 

  • Berx G, Becker KF, Hofler H, van Roy F (1998) Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 12:226–237. doi:10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D

    Article  PubMed  CAS  Google Scholar 

  • Brooks-Wilson AR, Kaurah P, Suriano G, Leach S, Senz J, Grehan N, Butterfield YS, Jeyes J, Schinas J, Bacani J, Kelsey M, Ferreira P, MacGillivray B, MacLeod P, Micek M, Ford J, Foulkes W, Australie K, Greenberg C, LaPointe M, Gilpin C, Nikkel S, Gilchrist D, Hughes R, Jackson CE, Monaghan KG, Oliveira MJ, Seruca R, Gallinger S, Caldas C, Huntsman D (2004) Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41:508–517. doi:10.1136/jmg.2004.018275

    Article  PubMed  CAS  Google Scholar 

  • Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, Powell SM, Lewis FR, Huntsman DG, Pharoah PD, Jankowski JA, MacLeod P, Vogelsang H, Keller G, Park KG, Richards FM, Maher ER, Gayther SA, Oliveira C, Grehan N, Wight D, Seruca R, Roviello F, Ponder BA, Jackson CE (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36:873–880. doi:10.1136/jmg.36.12.873

    PubMed  CAS  Google Scholar 

  • 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 61:25–30. doi:10.1136/jcp.2006.043679

    Article  PubMed  CAS  Google Scholar 

  • Caron O, Schielke A, Svrcek M, Flejou JF, Garzon J, Olschwang S, Sezeur A (2008) Usefulness of prophylactic gastrectomy in a novel large hereditary diffuse gastric cancer (HDGC) family. Am J Gastroenterol 103:2160–2161. doi:10.1111/j.1572-0241.2008.01982_17.x

    Article  PubMed  Google Scholar 

  • Carvalho J, van Grieken NC, Pereira PM, Sousa S, Tijssen M, Buffart TE, Diosdado B, Grabsch H, Santos MA, Meijer G, Seruca R, Carvalho B, Oliveira C (2012) Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer. J Pathol 228:31–44. doi:10.1002/path.4032

    PubMed  CAS  Google Scholar 

  • Corso G, Pedrazzani C, Pinheiro H, Fernandes E, Marrelli D, Rinnovati A, Pascale V, Seruca R, Oliveira C, Roviello F (2011) E-cadherin genetic screening and clinico-pathologic characteristics of early onset gastric cancer. Eur J Cancer 47:631–639. doi:10.1016/j.ejca.2010.10.011

    Article  PubMed  CAS  Google Scholar 

  • Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, Roviello F, Oliveira C (2012) Somatic mutations and deletions of the E-cadherin gene predict poor survival of gastric cancer patients. J Clin Oncol 31(7):868–875. doi:10.1200/JCO.2012.44.4612

    Article  Google Scholar 

  • Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011) Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 12:167–178. doi:10.1038/nrg2933

    Article  PubMed  CAS  Google Scholar 

  • Dussaulx-Garin L, Blayau M, Pagenault M, Le Berre-Heresbach N, Raoul JL, Campion JP, David V, Bretagne JF (2001) A new mutation of E-cadherin gene in familial gastric linitis plastica cancer with extra-digestive dissemination. Eur J Gastroenterol Hepatol 13:711–715

    Article  PubMed  CAS  Google Scholar 

  • Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simoes M (2002) Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94:1680–1687. doi:10.1093/jnci/94.22.1680

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C (2010) Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 47:436–444. doi:10.1136/jmg.2009.074237

    Article  PubMed  CAS  Google Scholar 

  • Frebourg T, Oliveira C, Hochain P, Karam R, Manouvrier S, Graziadio C, Vekemans M, Hartmann A, Baert-Desurmont S, Alexandre C, Lejeune Dumoulin S, Marroni C, Martin C, Castedo S, Lovett M, Winston J, Machado JC, Attie T, Jabs EW, Cai J, Pellerin P, Triboulet JP, Scotte M, Le Pessot F, Hedouin A, Carneiro F, Blayau M, Seruca R (2006) Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer. J Med Genet 43:138–142. doi:10.1136/jmg.2005.031385

    Article  PubMed  CAS  Google Scholar 

  • Gayther SA, Gorringe KL, Ramus SJ, Huntsman D, Roviello F, Grehan N, Machado JC, Pinto E, Seruca R, Halling K, MacLeod P, Powell SM, Jackson CE, Ponder BA, Caldas C (1998) Identification of germ-line E-cadherin mutations in gastric cancer families of European origin. Cancer Res 58:4086–4089

    PubMed  CAS  Google Scholar 

  • Ghaffari SR, Dastan J, Rafati M, Sabokbar T (2009) Novel human pathological mutations. Gene symbol: CDH1. Disease: gastric cancer. Hum Genet 125:337

    PubMed  Google Scholar 

  • Grady WM, Willis J, Guilford PJ, Dunbier AK, Toro TT, Lynch H, Wiesner G, Ferguson K, Eng C, Park JG, Kim SJ, Markowitz S (2000) Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet 26:16–17. doi:10.1038/79120

    Article  PubMed  CAS  Google Scholar 

  • Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405. doi:10.1038/32918

    Article  PubMed  CAS  Google Scholar 

  • Guilford PJ, Hopkins JB, Grady WM, Markowitz SD, Willis J, Lynch H, Rajput A, Wiesner GL, Lindor NM, Burgart LJ, Toro TT, Lee D, Limacher JM, Shaw DW, Findlay MP, Reeve AE (1999) E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat 14:249–255. doi:10.1002/(SICI)1098-1004(1999)14:3<249::AID-HUMU8>3.0.CO;2–9

    Article  PubMed  CAS  Google Scholar 

  • Guilford P, Humar B, Blair V (2010) Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice. Gastric Cancer 13:1–10. doi:10.1007/s10120-009-0531-x

    Article  PubMed  CAS  Google Scholar 

  • Herranz N, Pasini D, Diaz VM, Franci C, Gutierrez A, Dave N, Escriva M, Hernandez-Munoz I, Di Croce L, Helin K, Garcia de Herreros A, Peiro S (2008) Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol Cell Biol 28:4772–4781. doi:10.1128/MCB.00323-08

    Article  PubMed  CAS  Google Scholar 

  • Humar B, Graziano F, Cascinu S, Catalano V, Ruzzo AM, Magnani M, Toro T, Burchill T, Futschik ME, Merriman T, Guilford P (2002) Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer. Oncogene 21:8192–8195. doi:10.1038/sj.onc.1205921

    Article  PubMed  CAS  Google Scholar 

  • Hurteau GJ, Carlson JA, Spivack SD, Brock GJ (2007) Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer Res 67:7972–7976. doi:10.1158/0008-5472.CAN-07-1058

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90. doi:10.3322/caac.20107

    Article  PubMed  Google Scholar 

  • Jiang Y, Wan YL, Wang ZJ, Zhao B, Zhu J, Huang YT (2004) Germline E-cadherin gene mutation screening in familial gastric cancer kindreds. Chin J Surg (Zhonghua wai ke za zhi) 42:914–917

    Google Scholar 

  • Jones EG (1964) Familial gastric cancer. N Z Med J 63:287–296

    PubMed  CAS  Google Scholar 

  • 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 (Journal international du cancer) 98:838–843. doi:10.1002/ijc.10258

    Article  CAS  Google Scholar 

  • Kaurah P, MacMillan A, Boyd N, Senz J, De Luca A, Chun N, Suriano G, Zaor S, Van Manen L, Gilpin C, Nikkel S, Connolly-Wilson M, Weissman S, Rubinstein WS, Sebold C, Greenstein R, Stroop J, Yim D, Panzini B, McKinnon W, Greenblatt M, Wirtzfeld D, Fontaine D, Coit D, Yoon S, Chung D, Lauwers G, Pizzuti A, Vaccaro C, Redal MA, Oliveira C, Tischkowitz M, Olschwang S, Gallinger S, Lynch H, Green J, Ford J, Pharoah P, Fernandez B, Huntsman D (2007) Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297:2360–2372. doi:10.1001/jama.297.21.2360

    Article  PubMed  CAS  Google Scholar 

  • Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S, Grundei T, Becker KF, Mueller J, Siewert JR, Hofler H (1999) Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am J Pathol 155:337–342. doi:10.1016/S0002-9440(10)65129-2

    Article  PubMed  CAS  Google Scholar 

  • Keller G, Vogelsang H, Becker I, Plaschke S, Ott K, Suriano G, Mateus AR, Seruca R, Biedermann K, Huntsman D, Doring C, Holinski-Feder E, Neutzling A, Siewert JR, Hofler H (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:e89. doi:10.1136/jmg.2003.015594

    Article  PubMed  CAS  Google Scholar 

  • Kluijt I, Siemerink EJ, Ausems MG, van Os TA, de Jong D, Simoes-Correia J, van Krieken JH, Ligtenberg MJ, Figueiredo J, van Riel E, Sijmons RH, Plukker JT, van Hillegersberg R, Dekker E, Oliveira C, Cats A, Hoogerbrugge N (2012) CDH1-Related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling. Int J Cancer 131:367–376. doi:10.1002/ijc.26398

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Lauwers GY, Carneiro F, Graham DY, Curado MP, Franceschi S, Montgomery E, Tatematsu M, T H (2010) Gastric carcinoma. In: WHO classification of tumors of the digestive system. IARC Press, Lyon, pp 48–68

    Google Scholar 

  • Lynch HT, Aldoss I, Lynch JF (2011) The identification and management of hereditary diffuse gastric cancer in a large Jordanian family. Fam Cancer 10:667–672. doi:10.1007/s10689-011-9463-9

    Article  PubMed  Google Scholar 

  • Machado JC, Oliveira C, Carvalho R, Soares P, Berx G, Caldas C, Seruca R, Carneiro F, Sobrinho-Simoes M (2001) E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene 20:1525–1528. doi:10.1038/sj.onc.1204234

    Article  PubMed  CAS  Google Scholar 

  • Masciari S, Larsson N, Senz J, Boyd N, Kaurah P, Kandel MJ, Harris LN, Pinheiro HC, Troussard A, Miron P, Tung N, Oliveira C, Collins L, Schnitt S, Garber JE, Huntsman D (2007) Germline E-cadherin mutations in familial lobular breast cancer. J Med Genet 44:726–731. doi:10.1136/jmg.2007.051268

    Article  PubMed  CAS  Google Scholar 

  • Mateus AR, Simoes-Correia J, Figueiredo J, Heindl S, Alves CC, Suriano G, Luber B, Seruca R (2009) E-cadherin mutations and cell motility: a genotype-phenotype correlation. Exp Cell Res 315:1393–1402. doi:10.1016/j.yexcr.2009.02.020

    Article  PubMed  CAS  Google Scholar 

  • Matsukuma KE, Mullins FM, Dietz L, Zehnder JL, Ford JM, Chun NM, Schrijver I (2010) Hereditary diffuse gastric cancer due to a previously undescribed CDH1 splice site mutation. Hum Pathol 41:1200–1203. doi:10.1016/j.humpath.2010.01.022

    Article  PubMed  CAS  Google Scholar 

  • Mayrbaeurl B, Keller G, Schauer W, Burgstaller S, Czompo M, Hoebling W, Knoflach P, Duba HC, Hoefler H, Thaler J (2010) Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members. Eur J Gastroenterol Hepatol 22:306–310. doi:10.1097/MEG.0b013e32832bab9a

    Article  PubMed  CAS  Google Scholar 

  • McGill TW, Downey EC, Westbrook J, Wade D, de la Garza J (1993) Gastric carcinoma in children. J Pediatr Surg 28:1620–1621. doi:10.1016/0022-3468(93)90120-A

    Article  PubMed  CAS  Google Scholar 

  • More H, Humar B, Weber W, Ward R, Christian A, Lintott C, Graziano F, Ruzzo AM, Acosta E, Boman B, Harlan M, Ferreira P, Seruca R, Suriano G, Guilford P (2007) Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene. Hum Mutat 28:203. doi:10.1002/humu.9473

    Article  PubMed  CAS  Google Scholar 

  • Mori M, Sugimachi K, Ohiwa T, Okamura T, Tamura S, Inokuchi K (1985) Early gastric carcinoma in Japanese patients under 30 years of age. Br J Surg 72:289–291

    Article  PubMed  CAS  Google Scholar 

  • Nakamura T, Yao T, Niho Y, Tsuneyoshi M (1999) A clinicopathological study in young patients with gastric carcinoma. J Surg Oncol 71:214–219. doi:10.1002/(SICI)1096-9098(199908)71:4<214::AID-JSO2>3.0.CO;2-D

    Article  PubMed  CAS  Google Scholar 

  • Oliveira C, Bordin MC, Grehan N, Huntsman D, Suriano G, Machado JC, Kiviluoto T, Aaltonen L, Jackson CE, Seruca R, Caldas C (2002) Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Hum Mutat 19:510–517. doi:10.1002/humu.10068

    Article  PubMed  CAS  Google Scholar 

  • Oliveira C, de Bruin J, Nabais S, Ligtenberg M, Moutinho C, Nagengast FM, Seruca R, van Krieken H, Carneiro F (2004a) Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour. Oncogene 23:2236–2240. doi:10.1038/sj.onc.1207335

    Article  PubMed  CAS  Google Scholar 

  • Oliveira C, Ferreira P, Nabais S, Campos L, Ferreira A, Cirnes L, Alves CC, Veiga I, Fragoso M, Regateiro F, Dias LM, Moreira H, Suriano G, Machado JC, Lopes C, Castedo S, Carneiro F, Seruca R (2004b) 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 40:1897–1903. doi:10.1016/j.ejca.2004.04.027

    Article  PubMed  CAS  Google Scholar 

  • Oliveira C, Sousa S, Pinheiro H, Karam R, Bordeira-Carrico R, Senz J, Kaurah P, Carvalho J, Pereira R, Gusmao L, Wen X, Cipriano MA, Yokota J, Carneiro F, Huntsman D, Seruca R (2009a) Quantification of epigenetic and genetic 2nd hits in CDH1 during hereditary diffuse gastric cancer syndrome progression. Gastroenterology 136:2137–2148. doi:10.1053/j.gastro.2009.02.065

    Article  PubMed  CAS  Google Scholar 

  • Oliveira C, Senz J, Kaurah P, Pinheiro H, Sanges R, Haegert A, Corso G, Schouten J, Fitzgerald R, Vogelsang H, Keller G, Dwerryhouse S, Grimmer D, Chin SF, Yang HK, Jackson CE, Seruca R, Roviello F, Stupka E, Caldas C, Huntsman D (2009b) Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 18:1545–1555. doi:10.1093/hmg/ddp046

    Article  PubMed  CAS  Google Scholar 

  • Palli D, Galli M, Caporaso NE, Cipriani F, Decarli A, Saieva C, Fraumeni JF Jr, Buiatti E (1994) Family history and risk of stomach cancer in Italy. Cancer Epidemiol Biomarkers Prev 3:15–18

    PubMed  CAS  Google Scholar 

  • Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7:415–428. doi:10.1038/nrc2131

    Article  PubMed  CAS  Google Scholar 

  • Pharoah PD, Guilford P, Caldas C (2001) Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121:1348–1353. doi:10.1053/gast.2001.29611

    Article  PubMed  CAS  Google Scholar 

  • Pinheiro H, Bordeira-Carrico R, Seixas S, Carvalho J, Senz J, Oliveira P, Inacio P, Gusmao L, Rocha J, Huntsman D, Seruca R, Oliveira C (2010) Allele-specific CDH1 downregulation and hereditary diffuse gastric cancer. Hum Mol Genet 19:943–952. doi:10.1093/hmg/ddp537

    Article  PubMed  CAS  Google Scholar 

  • Pinho SS, Reis CA, Paredes J, Magalhaes AM, Ferreira AC, Figueiredo J, Xiaogang W, Carneiro F, Gartner F, Seruca R (2009) The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin. Hum Mol Genet 18:2599–2608. doi:10.1093/hmg/ddp194

    Article  PubMed  CAS  Google Scholar 

  • Richards FM, McKee SA, Rajpar MH, Cole TR, Evans DG, Jankowski JA, McKeown C, Sanders DS, Maher ER (1999) Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet 8:607–610. doi:10.1093/hmg/8.4.607

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Sanjuan JC, Fontalba A, Mayorga M, Bordin MC, Hyland SJ, Trugeda S, Garcia RA, Gomez-Fleitas M, Fernandez F, Caldas C, Fernandez-Luna JL (2006) A novel mutation in the E-cadherin gene in the first family with hereditary diffuse gastric cancer reported in Spain. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 32:1110–1113. doi:10.1016/j.ejso.2006.06.006

    Article  CAS  Google Scholar 

  • Rogers WM, Dobo E, Norton JA, Van Dam J, Jeffrey RB, Huntsman DG, Kingham K, Chun N, Ford JM, Longacre TA (2008) Risk-reducing total gastrectomy for germline mutations in E-cadherin (CDH1): pathologic findings with clinical implications. Am J Surg Pathol 32:799–809. doi:10.1097/PAS.0b013e31815e7f1a

    Article  PubMed  Google Scholar 

  • Roviello F, Corso G, Pedrazzani C, Marrelli D, De Falco G, Berardi A, Garosi L, Suriano G, Vindigni C, De Stefano A, Leoncini L, Seruca R, Pinto E (2007) Hereditary diffuse gastric cancer and E-cadherin: description of the first germline mutation in an Italian family. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 33:448–451. doi:10.1016/j.ejso.2006.10.028

    Article  CAS  Google Scholar 

  • Salahshor S, Hou H, Diep CB, Loukola A, Zhang H, Liu T, Chen J, Iselius L, Rubio C, Lothe RA, Aaltonen L, Sun XF, Lindmark G, Lindblom A (2001) A germline E-cadherin mutation in a family with gastric and colon cancer. Int J Mol Med 8:439–443

    PubMed  CAS  Google Scholar 

  • Schrader KA, Masciari S, Boyd N, Wiyrick S, Kaurah P, Senz J, Burke W, Lynch HT, Garber JE, Huntsman DG (2008) Hereditary diffuse gastric cancer: association with lobular breast cancer. Fam Cancer 7:73–82. doi:10.1007/s10689-007-9172-6

    Article  PubMed  Google Scholar 

  • Schrader KA, Masciari S, Boyd N, Salamanca C, Senz J, Saunders DN, Yorida E, Maines-Bandiera S, Kaurah P, Tung N, Robson ME, Ryan PD, Olopade OI, Domchek SM, Ford J, Isaacs C, Brown P, Balmana J, Razzak AR, Miron P, Coffey K, Terry MB, John EM, Andrulis IL, Knight JA, O’Malley FP, Daly M, Bender P, Moore R, Southey MC, Hopper JL, Garber JE, Huntsman DG (2011) Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers. J Med Genet 48:64–68. doi:10.1136/jmg.2010.079814

    Article  PubMed  CAS  Google Scholar 

  • Shah MA, Salo-Mullen E, Stadler Z, Ruggeri JM, Mirander M, Pristyazhnyuk Y, Zhang L (2012) De novo CDH1 mutation in a family presenting with early-onset diffuse gastric cancer. Clin Genet 82:283–287. doi:10.1111/j.1399-0004.2011.01744.x

    Article  PubMed  CAS  Google Scholar 

  • Shinmura K, Kohno T, Takahashi M, Sasaki A, Ochiai A, Guilford P, Hunter A, Reeve AE, Sugimura H, Yamaguchi N, Yokota J (1999) Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations. Carcinogenesis 20:1127–1131. doi:10.1093/carcin/20.6.1127

    Article  PubMed  CAS  Google Scholar 

  • Simoes-Correia J, Figueiredo J, Oliveira C, van Hengel J, Seruca R, van Roy F, Suriano G (2008) Endoplasmic reticulum quality control: a new mechanism of E-cadherin regulation and its implication in cancer. Hum Mol Genet 17:3566–3576. doi:10.1093/hmg/ddn249

    Article  PubMed  CAS  Google Scholar 

  • Simoes-Correia J, Figueiredo J, Lopes R, Stricher F, Oliveira C, Serrano L, Seruca R (2012) E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer. PLoS One 7:e33783. doi:10.1371/journal.pone.0033783

    Article  PubMed  CAS  Google Scholar 

  • Suriano G, Oliveira C, Ferreira P, Machado JC, Bordin MC, De Wever O, Bruyneel EA, Moguilevsky N, Grehan N, Porter TR, Richards FM, Hruban RH, Roviello F, Huntsman D, Mareel M, Carneiro F, Caldas C, Seruca R (2003) Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands. Hum Mol Genet 12:575–582. doi:10.1093/hmg/ddg048

    Article  PubMed  CAS  Google Scholar 

  • Suriano G, Yew S, Ferreira P, Senz J, Kaurah P, Ford JM, Longacre TA, Norton JA, Chun N, Young S, Oliveira MJ, Macgillivray B, Rao A, Sears D, Jackson CE, Boyd J, Yee C, Deters C, Pai GS, Hammond LS, McGivern BJ, Medgyesy D, Sartz D, Arun B, Oelschlager BK, Upton MP, Neufeld-Kaiser W, Silva OE, Donenberg TR, Kooby DA, Sharma S, Jonsson BA, Gronberg H, Gallinger S, Seruca R, Lynch H, Huntsman DG (2005) Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management. Clin Cancer Res 11:5401–5409. doi:10.1158/1078-0432.CCR-05-0247

    Article  PubMed  CAS  Google Scholar 

  • Vleminckx K, Vakaet L Jr, Mareel M, Fiers W, van Roy F (1991) Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66:107–119. doi:10.1016/0092-8674(91)90143-M

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Song JP, Ikeda M, Shinmura K, Yokota J, Sugimura H (2003) Ile-Leu substitution (I415L) in germline E-cadherin gene (CDH1) in Japanese familial gastric cancer. Jpn J Clin Oncol 33:17–20. doi:10.1093/jjco/hyg002

    Article  PubMed  CAS  Google Scholar 

  • Wilcox R, Perpich M, Noffsinger A, Posner MC, Cooper K (2011) Hereditary diffuse gastric cancer: multidisciplinary case report with review of the literature. Pathol Res Int 2011:845821. doi:10.4061/2011/845821

    Google Scholar 

  • Xie ZM, Li LS, Laquet C, Penault-Llorca F, Uhrhammer N, Xie XM, Bignon YJ (2011) Germline mutations of the E-cadherin gene in families with inherited invasive lobular breast carcinoma but no diffuse gastric cancer. Cancer 117:3112–3117. doi:10.1002/cncr.25876

    Article  PubMed  CAS  Google Scholar 

  • Yabuta T, Shinmura K, Tani M, Yamaguchi S, Yoshimura K, Katai H, Nakajima T, Mochiki E, Tsujinaka T, Takami M, Hirose K, Yamaguchi A, Takenoshita S, Yokota J (2002) E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer. Int J Cancer 101:434–441. doi:10.1002/ijc.10633

    Article  PubMed  CAS  Google Scholar 

  • 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 44:177–180. doi:10.1007/s100380050137

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Liu X, Fan Y, Ding J, Xu A, Zhou X, Hu X, Zhu M, Zhang X, Li S, Wu J, Cao H, Li J, Wang Y (2006) Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China. Int J Cancer (Journal international du cancer) 119:2592–2596. doi:10.1002/ijc.22206

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cancer Genetics, Expression Regulation in Cancer Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias S/N, 4200-465, Porto, Portugal

    Joana Carvalho Ph.D. & Hugo Pinheiro Ph.D.

  2. Expression Regulation in Cancer Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias S/N, 4200-465, Porto, Portugal

    Carla Oliveira Ph.D.

  3. Faculty of Medicine, University of Porto, Porto, Portugal

    Carla Oliveira Ph.D.

Authors
  1. Joana Carvalho Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hugo Pinheiro Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carla Oliveira Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carla Oliveira Ph.D. .

Editor information

Editors and Affiliations

  1. Dept. of Medical, Surgical Sciences, and Neurosciences, University of Siena, viale Bracci, Siena, 53100, Italy

    Giovanni Corso

  2. Dept. of Medical, Surgical Sciences, and Neurosciences, University of Siena, Via Banchi di Sotto 55, Siena, 53100, Italy

    Franco Roviello

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Carvalho, J., Pinheiro, H., Oliveira, C. (2013). E-Cadherin Germline Mutations. In: Corso, G., Roviello, F. (eds) Spotlight on Familial and Hereditary Gastric Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6570-2_5

Download citation

Publish with us

Policies and ethics

Search

Navigation