E-cadherin gene mutations provide clues to diffuse type gastric carcinomas.

摘要: Abstract The calcium-dependent homophilic cell adhesion molecule and candidate suppressor gene, E (epithelial)-cadherin, plays a major role in the organization integrity of most epithelial tissues. Diffusely growing gastric carcinomas show markedly reduced cell-to-cell interactions. We speculated that mutations E-cadherin gene may be responsible for scattered phenotype this type carcinoma. For reason we have examined 26 diffuse type, 20 intestinal 7 mixed (Lauren9s classification) at DNA, RNA, protein levels. Reverse transcription polymerase chain reaction direct sequencing amplified complementary DNA fragments revealed inframe skipping either exon 8 or 9 10 patients with tumors an deletion one patient carcinoma; both exons encode putative calcium binding domains. These alterations were not seen nontumorous Splice site deletions identified six these patients, eliminating possibility alternative splicing mechanisms. Five splice confirmed as somatic mutations. Non-splice observed three tumors, namely 69-base pair two point mutations, which destroys region. Immunohistochemical evaluation showed immunoreactivity lymph node metastases expressing abnormal mRNA. allelic status was analyzed patient, revealing loss heterozygosity retention mutated allele. Overall, 50% (13 26) 14% (1 7) carcinomas. In contrast, silent (not changing amino acid sequence) detected type. Our study provides strong vivo evidence contribute to development diffusely support tumor/metastasis hypothesis.