The online version of this article (doi:10.1186/1897-4287-12-17) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
ALV performed the high-resolution melting and sequence analysis and reviewed the manuscript, SR performed the genotyping of the A617T variant and reviewed the manuscript, CDS oversaw collection of all patient samples and reviewed the manuscript, REE designed the project, performed data analysis and wrote the manuscript. All authors read and approved the final manuscript.
Loss of cadherin 1 (CDH1) expression, which is normally involved in cell adhesion and maintenance of tissue architecture, is a hallmark of invasive lobular carcinoma (ILCA). Because hereditary cancers may require different risk reduction, counseling and treatment options than sporadic cancer, it is critical to determine the prevalence of germline CDH1 mutations in patients with ILCA.
All patients with ILCA (n = 100) previously enrolled in the Clinical Breast Care Project were identified. Genomic DNA was isolated from peripheral blood samples and DNA variants were detected for each exon of CDH1 using high-resolution melting technology followed by direct sequencing.
Within the 100 samples screened, four nonsynonymous variants were detected: A592T in one Hispanic patient, A617T in two patients, both African American, P825L in a Causasian patient whose grandmother had stomach cancer, and G879S in a Caucasian patient. Further evaluation of A617T in an additional 165 African American patients found that 11 patients, none with ILCA, carried this variant including one patient who was homozygous for the variant.
CDH1 mutations are infrequent in patients with ILCA, and the variants that were detected have been classified as non-pathogenic. These data suggest that ILCA does not have a significant hereditary component and do not support CDH1 gene mutation testing in patients with ILCA.
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Borst MJ, Ingold JA: Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. Surgery 1993, 114: 637–641. PubMed
Fisher ER, Gregorio RM, Fisher B, Redmond C, Vellios F, Sommers SC: The pathology of invasive breast cancer: a syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4). Cancer 1975, 36: 1–85. 10.1002/1097-0142(197507)36:1<1::AID-CNCR2820360102>3.0.CO;2-4 CrossRefPubMed
Lesser ML, Rosen PP, Kinne DW: Multicentricity and bilaterality in invasive breast carcinoma. Surgery 1982, 91: 234–240. PubMed
Paredes J, Figueiredo J, Albergaria A, Oliverira P, Carvalho J, Ribeiro AS, Caldeira J, Costa AM, Simoes-Correia J, Oliveira MJ, Pinheiro H, Pinho SS, Mateus R, Reis CA, Leite M, Ferdandes MS, Schmitt F, Carneiro F, Figueiredo C, Oiveira C, Seruca R: Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochem Biophys Res Commun 1826, 2012: 297–311.
Fitzgerald RC, Hardwick R, Huntsman D, Cameiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C, International Gastric Cancer Linkage Consortium: Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 2010, 47: 436–444. 10.1136/jmg.2009.074237 CrossRefPubMedPubMedCentral
American Joint Committee on Cancer: AJCC Cancer Staging Manual. 7th edition. New York: Springer; 2010. CrossRef
Silver DP: PARP Inhibition in Triple Negative Breast Cancer. 2011. 8 November, 2011
Sikora MJ, Cooper KL, Bahreini A, Luthra S, Wang G, Chandran UR, Davidson NE, Dabbs DJ, Welm AL, Oesterreich S: Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response. Cancer Res 2014, 74: 1463–1474. 10.1158/0008-5472.CAN-13-2779 CrossRefPubMedPubMedCentral
Kluijt I, Sijmons RH, Hoogerbrugge N, Plukker JT, de Jong D, Van Krieken JH, van Hillegersberg RL, Ligtenberg M, Bleiker E, Cats A, Dutch Working Group on Hereditary Gastric Cance: Familial gastric cancer: guidelines for diagnosis, treatment and periodic surveillance. Fam Cancer 2012, 11: 363–369. 10.1007/s10689-012-9521-y CrossRefPubMed
Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility J Clin Oncol 1996, 14: 1730–1736.
Garziera M, Canzoneiri V, Cannizzaro R, Geremia S, Caggiari L, De Zorzi M, Maiero S, Orzes E, Perin T, Zanussi S, de Paoli P, De Re V: Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer. PloS ONE 2013, 8: e77035. 10.1371/journal.pone.0077035 CrossRefPubMedPubMedCentral
Risinger JI, Berchuck A, Kohler MF, Boyd J: Mutations of the E-cadherin gene in human gynecologic cancers. Nat Genet 2014, 7: 98–102. CrossRef
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: Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands. Hum Mol Genet 2014, 12: 575–582. CrossRef
Suriano G, Oliveira MJ, Huntsman D, Mateus AR, Ferreira P, Casares F, Oliveira C, Cameiro F, Machado JC: E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells. Hum Mol Genet 2003, 12: 3007–3016. 10.1093/hmg/ddg316 CrossRefPubMed
Oliveira C, Senz J, Kaurah P, Pihheiro 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: Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 2009, 18: 1545–1555. 10.1093/hmg/ddp046 CrossRefPubMedPubMedCentral
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, Issacs 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, kConFab , Moore R, et al.: Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers. J Med Genet 2011, 48: 64–68. 10.1136/jmg.2010.079814 CrossRefPubMed
- Sequence-based detection of mutations in cadherin 1 to determine the prevalence of germline mutations in patients with invasive lobular carcinoma of the breast
Allyson L Valente
Craig D Shriver
Rachel E Ellsworth
- BioMed Central
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