Zusammenfassung
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.
- adult
- aged
- brca2_protein
- breast_neoplasms,_etiology/genetics
- cadherins,_genetics
- carcinoma,_ductal,_breast,_genetics
- dna_mutational_analysis
- dna_primers,_chemistry
- female
- genes,_brca1,_genetics
- germ-line_mutation
- humans
- loss_of_heterozygosity
- male
- middle_aged
- mutation,_missense
- neoplasm_proteins,_genetics
- pedigree
- polymerase_chain_reaction
- polymorphism,_single-stranded_conformational
- restriction_mapping
- transcription_factors,_genetics
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