A KRAB zinc finger protein gene is the potential target of 19q13 translocation in benign thyroid tumors

Abstract

In an attempt to identify the target gene of specific translocations involving chromosomal band 19q13 in benign follicular thyroid tumors, we have used two cell lines derived from benign thyroid tumors showing translocations with 19q13 breakpoints for fluorescence in situ hybridization mapping studies with cosmid and PAC clones located in a 400-kbp region. The breakpoints of the chromosome 19 abnormalities mapped within a 140-kb segment covered by a single PAC clone. Sequencing of part of this PAC clone allowed us to establish the cDNA sequence and the genomic structure of a candidate gene located in close vicinity to the breakpoints. The gene that we tentatively refer to as RITA (rearranged in thyroid adenomas) belongs to the KRAB zinc finger protein coding genes. From our results we have concluded that in the two cell lines investigated the breaks have occurred either within the 5' untranslated region of RITA or in its close 5' vicinity. By Northern blot analyses two transcripts of about 4.7 kbp and 5 kbp were detected in normal thyroid tissue as well as in other normal tissues tested. An additional 2.1-kbp transcript was found only in testicular tissue. In contrast to all normal tissues, both cell lines with 19q aberrations expressed larger transcripts of approximately 5.5 kbp and 6.2 kbp. From the close vicinity to the breakpoint region, the expression patterns of the gene, and its type, we consider RITA a strong candidate target gene of the specific 19q aberrations in benign thyroid tumors.