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Erschienen in: Breast Cancer Research 1/2001

01.02.2001 | Commentary

E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer?

verfasst von: Anne-Marie Cleton-Jansen

Erschienen in: Breast Cancer Research | Ausgabe 1/2001

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Abstract

Loss of heterozygosity at the long arm of chromosome 16 is one of the most frequent genetic events in breast cancer. In the search for tumour suppressor genes that are the target of loss of heterozygosity at 16q, the E-cadherin gene CDH1 was unveiled by the identification of truncating mutations in the retained copy. However, only lobular tumours showed E-cadherin mutations. Whereas investigations are still devoted to finding the target genes in the more frequent ductal breast cancers, other studies suspect the E-cadherin gene to also be the target in this tumour type. The present article discusses the plausibility of those two lines of thought.
Literatur
1.
Zurück zum Zitat Vleminckx K, Kemler R: Cadherins and tissue formation: integrating adhesion and signaling. Bioessays. 1999, 21: 211-220. 10.1002/(SICI)1521-1878(199903)21:3<211::AID-BIES5>3.0.CO;2-P.CrossRefPubMed Vleminckx K, Kemler R: Cadherins and tissue formation: integrating adhesion and signaling. Bioessays. 1999, 21: 211-220. 10.1002/(SICI)1521-1878(199903)21:3<211::AID-BIES5>3.0.CO;2-P.CrossRefPubMed
2.
Zurück zum Zitat Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hiro-hashi S: Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA. 1995, 92: 7416-7419.CrossRefPubMedPubMedCentral Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hiro-hashi S: Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA. 1995, 92: 7416-7419.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarrard DF, Isaacs WB, Pitha PM, Davidson NE, Baylin SB: E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 1995, 55: 5195-5199.PubMed Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarrard DF, Isaacs WB, Pitha PM, Davidson NE, Baylin SB: E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 1995, 55: 5195-5199.PubMed
4.
Zurück zum Zitat Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia DH: The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000, 2: 84-89. 10.1038/35000034.CrossRefPubMed Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia DH: The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000, 2: 84-89. 10.1038/35000034.CrossRefPubMed
5.
Zurück zum Zitat Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, Van Roy F: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001, 7: 1267-1278. 10.1016/S1097-2765(01)00260-X.CrossRefPubMed Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, Van Roy F: The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001, 7: 1267-1278. 10.1016/S1097-2765(01)00260-X.CrossRefPubMed
6.
Zurück zum Zitat Tan C, Costello P, Sanghera J, Dominguez D, Baulida J, De Herreros AG, Dedhar S: Inhibition of integrin linked kinase (ILK) suppresses beta-catenin–Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells. Oncogene. 2001, 20: 133-140. 10.1038/sj.onc.1204052.CrossRefPubMed Tan C, Costello P, Sanghera J, Dominguez D, Baulida J, De Herreros AG, Dedhar S: Inhibition of integrin linked kinase (ILK) suppresses beta-catenin–Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells. Oncogene. 2001, 20: 133-140. 10.1038/sj.onc.1204052.CrossRefPubMed
7.
Zurück zum Zitat Berx G, Becker KF, Hofler H, Van Roy F: Mutations of the human E-cadherin (CDH1) gene. Hum Mutat. 1998, 12: 226-237. 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D.CrossRefPubMed Berx G, Becker KF, Hofler H, Van Roy F: Mutations of the human E-cadherin (CDH1) gene. Hum Mutat. 1998, 12: 226-237. 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D.CrossRefPubMed
8.
Zurück zum Zitat Berx G, Cleton-Jansen AM, Strumane K, De Leeuw WJF, Nollet F, Van Roy F, Cornelisse C: E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene. 1996, 13: 1919-1925.PubMed Berx G, Cleton-Jansen AM, Strumane K, De Leeuw WJF, Nollet F, Van Roy F, Cornelisse C: E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene. 1996, 13: 1919-1925.PubMed
9.
Zurück zum Zitat Berx G, Cleton-Jansen AM, Nollet F, De Leeuw WJF, Van de Vijver MJ, Cornelisse C, Van Roy F: E-cadherin is a tumour invasion suppressor gene mutated in human lobular breast cancers. EMBO J. 1995, 14: 6107-6115.PubMedPubMedCentral Berx G, Cleton-Jansen AM, Nollet F, De Leeuw WJF, Van de Vijver MJ, Cornelisse C, Van Roy F: E-cadherin is a tumour invasion suppressor gene mutated in human lobular breast cancers. EMBO J. 1995, 14: 6107-6115.PubMedPubMedCentral
10.
Zurück zum Zitat Jones PA, Laird PW: Cancer epigenetics comes of age. Nat Genet. 1999, 21: 163-167. 10.1038/5947.CrossRefPubMed Jones PA, Laird PW: Cancer epigenetics comes of age. Nat Genet. 1999, 21: 163-167. 10.1038/5947.CrossRefPubMed
11.
Zurück zum Zitat Cleton-Jansen AM, Callen DF, Seshadri R, Goldup S, McCallum B, Crawford J, Powell JA, Settasatian C, van Beerendonk H, Moer-land EW, Smit VT, Harris WH, Millis R, Morgan NV, Barnes D, Mathew CG, Cornelisse CJ: Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions. Cancer Res. 2001, 61: 1171-1177.PubMed Cleton-Jansen AM, Callen DF, Seshadri R, Goldup S, McCallum B, Crawford J, Powell JA, Settasatian C, van Beerendonk H, Moer-land EW, Smit VT, Harris WH, Millis R, Morgan NV, Barnes D, Mathew CG, Cornelisse CJ: Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions. Cancer Res. 2001, 61: 1171-1177.PubMed
12.
Zurück zum Zitat Tischfield JA: Loss of heterozygosity or: how I learned to stop worrying and love mitotic recombination. Am J Hum Genet. 1997, 61: 995-999. 10.1086/301617.CrossRefPubMedPubMedCentral Tischfield JA: Loss of heterozygosity or: how I learned to stop worrying and love mitotic recombination. Am J Hum Genet. 1997, 61: 995-999. 10.1086/301617.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Devilee P, Cleton-Jansen AM, Cornelisse CJ: Ever since Knudson. Trends Genet. 2001, 17: 569-573. 10.1016/S0168-9525(01)02416-7.CrossRefPubMed Devilee P, Cleton-Jansen AM, Cornelisse CJ: Ever since Knudson. Trends Genet. 2001, 17: 569-573. 10.1016/S0168-9525(01)02416-7.CrossRefPubMed
15.
Zurück zum Zitat De Leeuw WJ, Berx G, Vos CB, Peterse JL, Van de Vijver MJ, Litvinov S, Van Roy F, Cornelisse CJ, Cleton-Jansen AM: Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997, 183: 404-411. 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.CrossRefPubMed De Leeuw WJ, Berx G, Vos CB, Peterse JL, Van de Vijver MJ, Litvinov S, Van Roy F, Cornelisse CJ, Cleton-Jansen AM: Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997, 183: 404-411. 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.CrossRefPubMed
16.
Zurück zum Zitat Vos CB, Cleton-Jansen AM, Berx G, De Leeuw WJ, ter Haar NT, Van Roy F, Cornelisse CJ, Peterse JL, Van de Vijver MJ: E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis. Br J Cancer. 1997, 76: 1131-1133.CrossRefPubMedPubMedCentral Vos CB, Cleton-Jansen AM, Berx G, De Leeuw WJ, ter Haar NT, Van Roy F, Cornelisse CJ, Peterse JL, Van de Vijver MJ: E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis. Br J Cancer. 1997, 76: 1131-1133.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Vos CBJ, ter Haar NT, Rosenberg C, Peterse JL, Cleton-Jansen A-M, Cornelisse CJ, Van de Vijver MJ: Genetic alterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histological type. Br J Cancer. 1999, 81: 1410-1418. 10.1038/sj.bjc.6693372.CrossRefPubMedPubMedCentral Vos CBJ, ter Haar NT, Rosenberg C, Peterse JL, Cleton-Jansen A-M, Cornelisse CJ, Van de Vijver MJ: Genetic alterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histological type. Br J Cancer. 1999, 81: 1410-1418. 10.1038/sj.bjc.6693372.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Vleminckx K, Vakaet L, Mareel M, Fiers W, Van Roy F: Genetic manipulations of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991, 66: 107-119.CrossRefPubMed Vleminckx K, Vakaet L, Mareel M, Fiers W, Van Roy F: Genetic manipulations of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991, 66: 107-119.CrossRefPubMed
19.
Zurück zum Zitat Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G: A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 1998, 392: 190-193. 10.1038/32433.CrossRefPubMed Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G: A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 1998, 392: 190-193. 10.1038/32433.CrossRefPubMed
20.
Zurück zum Zitat Birchmeier W, Behrens J: Cadherin expression in carcinomas: Role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994, 1198: 11-26. 10.1016/0304-419X(94)90003-5.PubMed Birchmeier W, Behrens J: Cadherin expression in carcinomas: Role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994, 1198: 11-26. 10.1016/0304-419X(94)90003-5.PubMed
21.
Zurück zum Zitat Lakhani SR, Collins N, Sloane JP, Stratton MR: Loss of heterozy-gosity in lobular carcinoma in situ of the breast. J Clin Pathol. 1995, 48M: M74-M78. Lakhani SR, Collins N, Sloane JP, Stratton MR: Loss of heterozy-gosity in lobular carcinoma in situ of the breast. J Clin Pathol. 1995, 48M: M74-M78.
22.
Zurück zum Zitat Lakhani SR: The transition from hyperplasia to invasive carcinoma of the breast. J Pathol. 1999, 187: 272-278. 10.1002/(SICI)1096-9896(199902)187:3<272::AID-PATH265>3.0.CO;2-2.CrossRefPubMed Lakhani SR: The transition from hyperplasia to invasive carcinoma of the breast. J Pathol. 1999, 187: 272-278. 10.1002/(SICI)1096-9896(199902)187:3<272::AID-PATH265>3.0.CO;2-2.CrossRefPubMed
23.
Zurück zum Zitat Roylance R, Gorman P, Harris W, Liebmann R, Barnes D, Hanby A, Sheer D: Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer. Cancer Res. 1999, 59: 1433-1436.PubMed Roylance R, Gorman P, Harris W, Liebmann R, Barnes D, Hanby A, Sheer D: Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer. Cancer Res. 1999, 59: 1433-1436.PubMed
24.
Zurück zum Zitat Buerger H, Simon R, Schafer KL, Diallo R, Littmann R, Poremba C, Van Diest PJ, Dockhorn-Dworniczak B, Bocker W: Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast. Mol Pathol. 2000, 53: 118-121. 10.1136/mp.53.3.118.CrossRefPubMedPubMedCentral Buerger H, Simon R, Schafer KL, Diallo R, Littmann R, Poremba C, Van Diest PJ, Dockhorn-Dworniczak B, Bocker W: Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast. Mol Pathol. 2000, 53: 118-121. 10.1136/mp.53.3.118.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE: E-cadherin germline mutations in familial gastric cancer. Nature. 1998, 392: 402-405. 10.1038/32918.CrossRefPubMed Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE: E-cadherin germline mutations in familial gastric cancer. Nature. 1998, 392: 402-405. 10.1038/32918.CrossRefPubMed
26.
Zurück zum Zitat Richards FM, McKee SA, Rajpar MH, Cole TR, Evans DG, Jankowski JA, McKeown C, Sanders DS, Maher ER: Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet. 1999, 8: 607-610. 10.1093/hmg/8.4.607.CrossRefPubMed Richards FM, McKee SA, Rajpar MH, Cole TR, Evans DG, Jankowski JA, McKeown C, Sanders DS, Maher ER: Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet. 1999, 8: 607-610. 10.1093/hmg/8.4.607.CrossRefPubMed
27.
Zurück zum Zitat Rahman N, Stone JG, Coleman G, Gusterson B, Seal S, Marossy A, Lakhani SR, Ward A, Nash A, McKinna A, A'Hern R, Stratton MR, Houlston RS: Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene. Br J Cancer. 2000, 82: 568-570. 10.1054/bjoc.1999.0965.CrossRefPubMedPubMedCentral Rahman N, Stone JG, Coleman G, Gusterson B, Seal S, Marossy A, Lakhani SR, Ward A, Nash A, McKinna A, A'Hern R, Stratton MR, Houlston RS: Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene. Br J Cancer. 2000, 82: 568-570. 10.1054/bjoc.1999.0965.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Grady WM, Willis J, Guilford PJ, Dunbier AK, Toro TT, Lynch H, Wiesner G, Ferguson K, Eng C, Park JG, Kim SJ, Markowitz S: Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000, 26: 16-17. 10.1038/79120.CrossRefPubMed Grady WM, Willis J, Guilford PJ, Dunbier AK, Toro TT, Lynch H, Wiesner G, Ferguson K, Eng C, Park JG, Kim SJ, Markowitz S: Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000, 26: 16-17. 10.1038/79120.CrossRefPubMed
Metadaten
Titel
E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer?
verfasst von
Anne-Marie Cleton-Jansen
Publikationsdatum
01.02.2001
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 1/2001
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr416

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