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

In an attempt to identify the target gene of specific translocations involv ing chromosomal band 19q13 in benign follicular thyroid tumors, we have use d two cell lines derived from benign thyroid tumors showing translocations with 19q13 breakpoints for fluorescence in situ hybridization mapping studi es 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 b y a single PAC clone. Sequencing of part of this PAC clone allowed us to es tablish the cDNA sequence and the genomic structure of a candidate gene loc ated in close vicinity to the breakpoints. The gene that we tentatively ref er to as RITA (rearranged in thyroid adenomas) belongs to the KRAB zinc fin ger protein coding genes. From our results we have concluded that in the tw o cell lines investigated the breaks have occurred either within the 5' unt ranslated region of RITA or in its close 5' vicinity. By Northern blot anal yses two transcripts of about 4.7 kbp and 5 kbp were detected in normal thy roid tissue as well as in other normal tissues tested. An additional 2.1-kb p 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 break point region, the expression patterns of the gene, and its type, we conside r RITA a strong candidate target gene of the specific 19q aberrations in be nign thyroid tumors. (C) 1999 Wiley-Liss, Inc.