Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer

We have studied a set of 40 human lobular breast cancers for loss of hetero zygosity (LOH) at various chromosome locations and for mutations in the cod ing region plus flanking intron sequences of the E-cadherin gene. We found a high frequency of LOH (100%, 31/31) at 16q21-q22.1. A significantly highe r level of LOH was detected in ductal breast tumours at chromosome arms 1p, 3p, 9p, 11q, 13q and 18q compared to lobular breast tumours. Furthermore, we found a significant association between LOH at 16 q containing the E-cad herin locus and lobular histological type. Six different somatic mutations were detected in the E-cadherin gene, of which three were insertions, two d eletions and one splice site mutation. Mutations were found in combination with LOH of the wild type E-cadherin locus and loss of or reduced E-cadheri n expression detected by immunohistochemistry. The mutations described here have not previously been reported. We compared LOH at different chromosome regions with E-cadherin gene mutations and founds significant association between LOH at 13q and E-cadherin gene mutations. A significant association was also detected between LOH at 13q and LOH at 7q and 11q. Moreover, we f ound a significant association between LOH at 3p and high S phase, LOH at 9 p and low ER and PSR content, LOH at 17p and aneuploidy. We conclude that L OH at 16q is the most frequent chromosome alteration and E-cadherin is a ty pical tumour suppressor gene in lobular breast cancer. (C) 1999 Cancer Rese arch Campaign.