Abstract
Chromosome rearrangements involving 12q13‐15 are frequent among several tumors, including pleomorphic adenomas. The common molecular target for these aberrations is the HMGA____2 gene, but various fusion partners of HMGA____2 have been reported in tumors. Here we report the identification of the WNT inhibitory factor 1 (WIF____1) gene as a novel HMGA____2 fusion partner in a salivary gland pleomorphic adenoma. In normal salivary gland tissue WIF____1 is expressed at a high level and HMGA____2 is not expressed. However, in the pleomorphic adenoma expressing the HMGA____2/WIF____1 fusion transcript, we observed re‐expression of HMGA____2 wild‐type transcripts and very low levels of WIF____1 expression. These data suggest a possible synergistic effect between upregulation of HMGA____2 and downregulation of WIF____1. We screened 13 additional benign and malignant salivary gland tumors and detected WIF____1 rearrangement in one out of two carcinomas ex‐pleomorphic adenoma analyzed. In this malignant tumor, the rearrangement of one WIF____1 allele coexists with loss of the other allele, a classic signature of a tumor suppressor gene. WIF1 is an antagonist of the Wnt signaling pathway, which plays a critical role in human cancer. In transgenic mouse models, Wnt activation leads to a high frequency of benign and malignant salivary gland tumors. To our knowledge, this is the first report suggesting that WIF____1 is a recurrent target in human salivary gland oncogenesis and that downregulation of WIF____1 plays a role in the development and/or progression of pleomorphic adenomas. © 2006 Wiley‐Liss, Inc.