CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk
✍ Scribed by Haixin Lei; Sara Sjöberg-Margolin; Sima Salahshor; Barbro Werelius; Eva Jandáková; Kari Hemminki; Annika Lindblom; Igor Vořechovský
- Book ID
- 102861680
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- French
- Weight
- 528 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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. © 2001 Wiley‐Liss, Inc.