CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk
CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk
Mutations and diminished expression of the E-cadherin gene (CDH1) have been identified in a number of epithelial malignancies. Although somatic CDH1 mutations were detected in lobular breast cancer with a frequency ranging from 10-56%, CDH1 alterations in more frequent ductal tumors appear to be rare. Here we have analyzed the coding region of CDH1 for mutations using denaturing high performance liquid chromatography and found 4 mutations in 83 ductal carcinomas (5%) and 3 mutations in 25 lobular carcinomas (12%). The germline of 13 patients with familial lobular tumors was also analyzed for mutations, but none were detected. In a case-control study, we also tested whether a variant adenine allele in the promoter polymorphism -161C-->A with a putative influence on the transcriptional activity of CDH1 in vitro confers any detectable risk of breast cancer. No significant difference in the allelic frequency between patients with breast cancer (326/1,152, 28.3%) and controls (190/696, 27.3%, p > 0.05; relative risk 1.05, 95% confidence interval 0.85-1.30) was found. A novel promoter polymorphism was identified at position -152, but the frequency of the variant cytosine allele was also similar in patients with breast cancer and controls (0.71% vs. 0.21%, p = 0.23). Transient transfection experiments using reporter constructs containing the nucleotide substitutions -161C/-152C and -161A/-152T showed only a slight decrease in the transcription activity compared to the wild-type construct. These results do not support CDH1 as a prominent low-penetrance cancer susceptibility gene, but indicate that CDH1 mutations contribute to the progression of both lobular and ductal tumors
E-cadherin, mutation, breast cancer, promoter, SNP
199-204
Lei, Haixin
24595b39-a4e6-4cfc-9354-5001b7f70d5a
Sjoberg-Margolin, Sara
0c58cb59-dc60-4033-9b84-cb6b2b3ab24c
Salahshor, Sima
2a5a0065-eea0-420e-8cd9-cb073df8f8ab
Werelius, Barbro
8c84d2fa-5816-4020-b24a-32841e456c52
Jandakova, Eva
ead6f933-c9e8-4545-9ca2-fd6a37ffec75
Hemminki, Kari
4ce7a3f5-a609-4efd-b87d-1e8d0f9fc191
Lindblom, Annika
855a20de-8712-44cb-9a0a-01d4176a666f
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
2002
Lei, Haixin
24595b39-a4e6-4cfc-9354-5001b7f70d5a
Sjoberg-Margolin, Sara
0c58cb59-dc60-4033-9b84-cb6b2b3ab24c
Salahshor, Sima
2a5a0065-eea0-420e-8cd9-cb073df8f8ab
Werelius, Barbro
8c84d2fa-5816-4020-b24a-32841e456c52
Jandakova, Eva
ead6f933-c9e8-4545-9ca2-fd6a37ffec75
Hemminki, Kari
4ce7a3f5-a609-4efd-b87d-1e8d0f9fc191
Lindblom, Annika
855a20de-8712-44cb-9a0a-01d4176a666f
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Lei, Haixin, Sjoberg-Margolin, Sara, Salahshor, Sima, Werelius, Barbro, Jandakova, Eva, Hemminki, Kari, Lindblom, Annika and Vorechovsky, Igor
(2002)
CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk.
International Journal of Cancer, 98 (2), .
(doi:10.1002/ijc.10176).
Abstract
Mutations and diminished expression of the E-cadherin gene (CDH1) have been identified in a number of epithelial malignancies. Although somatic CDH1 mutations were detected in lobular breast cancer with a frequency ranging from 10-56%, CDH1 alterations in more frequent ductal tumors appear to be rare. Here we have analyzed the coding region of CDH1 for mutations using denaturing high performance liquid chromatography and found 4 mutations in 83 ductal carcinomas (5%) and 3 mutations in 25 lobular carcinomas (12%). The germline of 13 patients with familial lobular tumors was also analyzed for mutations, but none were detected. In a case-control study, we also tested whether a variant adenine allele in the promoter polymorphism -161C-->A with a putative influence on the transcriptional activity of CDH1 in vitro confers any detectable risk of breast cancer. No significant difference in the allelic frequency between patients with breast cancer (326/1,152, 28.3%) and controls (190/696, 27.3%, p > 0.05; relative risk 1.05, 95% confidence interval 0.85-1.30) was found. A novel promoter polymorphism was identified at position -152, but the frequency of the variant cytosine allele was also similar in patients with breast cancer and controls (0.71% vs. 0.21%, p = 0.23). Transient transfection experiments using reporter constructs containing the nucleotide substitutions -161C/-152C and -161A/-152T showed only a slight decrease in the transcription activity compared to the wild-type construct. These results do not support CDH1 as a prominent low-penetrance cancer susceptibility gene, but indicate that CDH1 mutations contribute to the progression of both lobular and ductal tumors
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Published date: 2002
Keywords:
E-cadherin, mutation, breast cancer, promoter, SNP
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Local EPrints ID: 59980
URI: http://eprints.soton.ac.uk/id/eprint/59980
ISSN: 0020-7136
PURE UUID: d9070390-b557-4423-baf7-5d069381fe3c
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Date deposited: 05 Sep 2008
Last modified: 16 Mar 2024 03:32
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Author:
Haixin Lei
Author:
Sara Sjoberg-Margolin
Author:
Sima Salahshor
Author:
Barbro Werelius
Author:
Eva Jandakova
Author:
Kari Hemminki
Author:
Annika Lindblom
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