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Low frequency of E-cadherin alterations in familial breast cancer.

Salahshor S, Haixin L, Huo H, Kristensen VN, Loman N, Sjöberg-Margolin S, Borg A, Børresen-Dale AL, Vorechovsky I, Lindblom A - Breast Cancer Res. (2001)

Bottom Line: No pathogenic germline alterations were detected in these individuals.Another 10 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found.The frequencies of this alteration were similar in these groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.

ABSTRACT
In order to explore the possible role of E-cadherin in familial cancer, 19 familial breast cancer patients, whose tumours demonstrated loss of heterozygosity (LOH) at the E-cadherin locus, were screened for germline mutations. No pathogenic germline alterations were detected in these individuals. However, a somatic mutation was found (49-2A-->C) in one of the tumours. This tumour showed a pattern of both ductal and lobular histology. Another 10 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found. A missense mutation in exon 12 of E-cadherin (1774G-->A; Ala592Thr) was previously found in one family with diffuse gastric cancer, and colon and breast cancer. An allelic association study was performed to determine whether the Ala592Thr alteration predisposes to breast cancer. In total, we studied 484 familial breast cancer patients, 614 sporadic breast cancer patients and 497 control individuals. The frequencies of this alteration were similar in these groups. However, a correlation between the Ala592Thr alteration and ductal comedo-type tumour was seen. These results, together with previously reported studies, indicate that germline mutations and, more commonly, somatic mutations in E-cadherin may have an influence on the behaviour of the tumours, rather than predispose to breast cancer.

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Pedigrees of the four families with Ala592Thr missense alteration. BR, breast cancer; GA, gastric cancer; OV, ovarian cancer; GI, gastrointestinal cancer; AD, colonic adenomas; Endo, endometrial cancer; M, positive for the Ala592Thr variant; N, wild-type E-cadherin.
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Figure 1: Pedigrees of the four families with Ala592Thr missense alteration. BR, breast cancer; GA, gastric cancer; OV, ovarian cancer; GI, gastrointestinal cancer; AD, colonic adenomas; Endo, endometrial cancer; M, positive for the Ala592Thr variant; N, wild-type E-cadherin.

Mentions: In a previous study of a family with diffuse gastric cancer (Fig. 1a) (Salahshor S, et al, manuscript submitted), we identified an E-cadherin germline mutation that cosegregated with the disease. This missense mutation in exon 12 (Ala592Thr) was also detected in the index patient's mother, who had ductal breast cancer. In an attempt to clarify a possible role for the Ala592Thr alteration in predisposing to breast cancer, we screened for this specific alteration in different series of breast cancer patients and control individuals. In total, 1328 patients with sporadic or familial breast cancer and 497 control individuals were analyzed for this specific alteration.


Low frequency of E-cadherin alterations in familial breast cancer.

Salahshor S, Haixin L, Huo H, Kristensen VN, Loman N, Sjöberg-Margolin S, Borg A, Børresen-Dale AL, Vorechovsky I, Lindblom A - Breast Cancer Res. (2001)

Pedigrees of the four families with Ala592Thr missense alteration. BR, breast cancer; GA, gastric cancer; OV, ovarian cancer; GI, gastrointestinal cancer; AD, colonic adenomas; Endo, endometrial cancer; M, positive for the Ala592Thr variant; N, wild-type E-cadherin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30704&req=5

Figure 1: Pedigrees of the four families with Ala592Thr missense alteration. BR, breast cancer; GA, gastric cancer; OV, ovarian cancer; GI, gastrointestinal cancer; AD, colonic adenomas; Endo, endometrial cancer; M, positive for the Ala592Thr variant; N, wild-type E-cadherin.
Mentions: In a previous study of a family with diffuse gastric cancer (Fig. 1a) (Salahshor S, et al, manuscript submitted), we identified an E-cadherin germline mutation that cosegregated with the disease. This missense mutation in exon 12 (Ala592Thr) was also detected in the index patient's mother, who had ductal breast cancer. In an attempt to clarify a possible role for the Ala592Thr alteration in predisposing to breast cancer, we screened for this specific alteration in different series of breast cancer patients and control individuals. In total, 1328 patients with sporadic or familial breast cancer and 497 control individuals were analyzed for this specific alteration.

Bottom Line: No pathogenic germline alterations were detected in these individuals.Another 10 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found.The frequencies of this alteration were similar in these groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.

ABSTRACT
In order to explore the possible role of E-cadherin in familial cancer, 19 familial breast cancer patients, whose tumours demonstrated loss of heterozygosity (LOH) at the E-cadherin locus, were screened for germline mutations. No pathogenic germline alterations were detected in these individuals. However, a somatic mutation was found (49-2A-->C) in one of the tumours. This tumour showed a pattern of both ductal and lobular histology. Another 10 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found. A missense mutation in exon 12 of E-cadherin (1774G-->A; Ala592Thr) was previously found in one family with diffuse gastric cancer, and colon and breast cancer. An allelic association study was performed to determine whether the Ala592Thr alteration predisposes to breast cancer. In total, we studied 484 familial breast cancer patients, 614 sporadic breast cancer patients and 497 control individuals. The frequencies of this alteration were similar in these groups. However, a correlation between the Ala592Thr alteration and ductal comedo-type tumour was seen. These results, together with previously reported studies, indicate that germline mutations and, more commonly, somatic mutations in E-cadherin may have an influence on the behaviour of the tumours, rather than predispose to breast cancer.

Show MeSH
Related in: MedlinePlus