PMID- 7491517 OWN - NLM STAT- MEDLINE DCOM- 19960104 LR - 20211203 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 118 IP - 6 DP - 1995 Dec TI - Molecular and cytogenetic characterization of a t(1;10;21) translocation in the human papillary thyroid cancer cell line TPC-1 expressing the ret/H4 chimeric transcript. PG - 1018-23 AB - BACKGROUND: Activation of the ret proto-oncogene by three different chromosomal rearrangements occurs in up to 25% of papillary thyroid carcinomas. We developed a rapid screening technique to detect ret rearrangements in human interphase and metaphase cells on the basis of multicolor fluorescence in situ hybridization (FISH) of locus-specific DNA probes. METHODS: DNA from individual clones representing the respective ends of a yeast artificial chromosome (YAC) contig spanning the entire ret gene locus were labeled with either digoxigenin (visualized in red) or biotin (green) and hybridized to normal human lymphocytes and the papillary thyroid cancer cell line TPC-1 expressing the ret/H4 chimeric transcript. Further detailed analysis was performed with whole chromosome painting probes and locus-specific probes (YACs, P1s, DNA repeat probes) on tumor metaphase spreads. RESULTS: Hybridization of the YACs to unrearranged ret loci in normal human lymphocyte interphase nuclei showed two yellow domains because of probe overlap. Hybridization to TPC-1 interphase nuclei showed one yellow domain, and 1 red and 1 green domain separated by a large physical distance. Further analysis of metaphase spreads revealed a complex translocation t(1;10;21)(1pter > 1q31::21q22.1 > 21qter; 10q11.2 > 10pter::1q31 > 1qter; 21pter > 21q22.1;;10q21.2 > 10q11.2::10q21.2 > 10qter) and loss of the H4 gene locus on the nontranslocated chromosome 10. CONCLUSIONS: Break point spanning probes can reliably detect ret rearrangements in interphase nuclei. Locus-specific and whole chromosome painting probes can be used to further characterize complex rearrangements by fluorescence in situ hybridization to metaphase spreads. The papillary thyroid cancer cell line TPC-1 carries the paracentric inversion 10q, inv(10)(q11.2q21) and a complex t(1; 10; 21) translocation. Deletion of the H4 gene on the chromosome 10 not involved in the t(1; 10; 21) translocation suggests lack of normal H4 expression in the TPC-1 cell line. Further studies will have to address the role of the H4 gene product in tumor genesis and progression. FAU - Jossart, G H AU - Jossart GH AD - Department of Surgery, UCSF/Mount Zion Medical Center, USA. FAU - Greulich, K M AU - Greulich KM FAU - Siperstein, A E AU - Siperstein AE FAU - Duh, Q AU - Duh Q FAU - Clark, O H AU - Clark OH FAU - Weier, H U AU - Weier HU LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (DNA Probes) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) SB - IM MH - Carcinoma, Papillary/*genetics MH - Chimera MH - Chromosomes, Artificial, Yeast MH - *Chromosomes, Human, Pair 1 MH - *Chromosomes, Human, Pair 10 MH - *Chromosomes, Human, Pair 21 MH - DNA Probes MH - Humans MH - In Situ Hybridization, Fluorescence MH - Proto-Oncogene Mas MH - Thyroid Neoplasms/*genetics MH - *Translocation, Genetic MH - Tumor Cells, Cultured EDAT- 1995/12/01 00:00 MHDA- 1995/12/01 00:01 CRDT- 1995/12/01 00:00 PHST- 1995/12/01 00:00 [pubmed] PHST- 1995/12/01 00:01 [medline] PHST- 1995/12/01 00:00 [entrez] AID - S0039-6060(05)80108-4 [pii] AID - 10.1016/s0039-6060(05)80108-4 [doi] PST - ppublish SO - Surgery. 1995 Dec;118(6):1018-23. doi: 10.1016/s0039-6060(05)80108-4.