E-cadherin gene alterations in gastric cancers in different ethnic populations.

Introduction: A retrospective study of nucleotide sequence alterations in exons 7-9 of the E-cadherin gene and expression of E-cadherin and beta-catenin in gastric tumors from African American, Asian, Causcasian and Hispanic patients was carried out to determine differences potentially related to race/ethnicity in these groups.

Methods: Paraffin-embedded tissue sections archived at the Memorial Sloan Kettering Cancer Center were used for immunohistochemical staining of sections for membranous E-cadherin protein and nuclear localization of beta-catenin. DNA from tumor tissue extracted from the paraffin sections was used as template for amplification of the E-cadherin gene exonic regions.

Results: Sequence analyses of the high-frequency mutation region along E-cadherin exons 7-9 revealed a number sequence alterations in the patient group as a whole, mostly within exon 8. The alterations were mainly single nucleotide insertions, but a palindromic duplication of exon 8 in a Caucasian patient and several extragenic insertions in a Hispanic and an African American patient were also found. Nuclear localization of beta-catenin was correlated with inactivating sequence alterations in three patients.

Conclusions: Exon 8 was found to display the most extensive alterations in all the groups studied. As a group, the most extensive sequence alterations were found in tumors from Caucasian patients. A finding of potential significance as a biomarker related to ethnicity was a C insertion at nt 76,598 found independently in two African American patients.