Rippe Volkhard, Drieschner Norbert, Meiboom Maren, Murua Escobar Hugo, Bonk Ulrich, Belge Gazanfer, Bullerdiek Jörn
Center for Human Genetics, University of Bremen, Leobener Str. ZHG, D-28359 Bremen, Germany.
Oncogene. 2003 Sep 4;22(38):6111-4. doi: 10.1038/sj.onc.1206867.
Thyroid adenomas belong to the cytogenetically best investigated human epithelial tumors. Cytogenetic studies of about 450 benign lesions allow one to distinguish between different cytogenetic subgroups. Two chromosomal regions, that is, 19q13 and 2p21, are frequently rearranged in these tumors. Although 2p21 aberrations only account for about 10% of the benign thyroid tumors with clonal cytogenetic deviations, 2p21 rearrangements belong to the most common cytogenetic rearrangements in epithelial tumors due to the high frequency of these benign lesions. The 2p21 breakpoint region recently has been delineated to a region of 450 kbp, but the gene affected by the cytogenetic rearrangements still has escaped detection. Positional cloning and 3' RACE-PCR allowed us to clone that gene which we will refer to as thyroid adenoma associated (THADA) gene. In cells from two thyroid adenomas characterized by translocations t(2;20;3) (p21;q11.2;p25) and t(2;7)(p21;p15), respectively, we performed 3'-RACE-PCRs and found two fusions of THADA with a sequence derived from chromosome band 3p25 or with a sequence derived from chromosome band 7p15. The THADA gene spans roughly 365 kbp and, based on preliminary results, encodes a death receptor-interacting protein.
甲状腺腺瘤属于细胞遗传学研究最为深入的人类上皮性肿瘤。对约450例良性病变进行的细胞遗传学研究使人们能够区分不同的细胞遗传学亚组。在这些肿瘤中，两个染色体区域，即19q13和2p21，经常发生重排。虽然2p21畸变仅占具有克隆性细胞遗传学偏差的良性甲状腺肿瘤的约10%，但由于这些良性病变的高发性，2p21重排属于上皮性肿瘤中最常见的细胞遗传学重排。2p21断裂点区域最近已被划定为一个450 kbp的区域，但受细胞遗传学重排影响的基因仍未被发现。定位克隆和3' RACE-PCR使我们能够克隆该基因，我们将其称为甲状腺腺瘤相关（THADA）基因。在分别以易位t(2;20;3)(p21;q11.2;p25)和t(2;7)(p21;p15)为特征的两个甲状腺腺瘤细胞中，我们进行了3'-RACE-PCR，发现THADA与来自染色体带3p25的序列或与来自染色体带7p15的序列有两种融合。THADA基因大约跨越365 kbp，根据初步结果，它编码一种死亡受体相互作用蛋白。
