The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8
The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8
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DOI：
10.1073/pnas.95.16.9572
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Drabkin, HA
中科院分区：
文献类型：
--
作者：
Gemmill, RM;West, JD;Drabkin, HA
3;本文报道了一个具有典型遗传性肾癌特征的家系，该家系存在t（3;8）（p14.2;q24.1）染色体易位。然而，FHIT与肾脏或其他恶性肿瘤有因果关系的证据存在争议。我们现在表明，8q24.1断点区域编码一个664-aa的多跨膜蛋白，TRC 8，与遗传性基底细胞癌/节段极性基因相似，修补。这种相似性涉及两个区域的补丁，推定的甾醇敏感结构域和第二个细胞外环，参与音刺猬的结合。在3;8易位，TRC 8融合到FHIT，并在甾醇敏感结构域内被破坏。相反，FHIT编码区被维持和表达。在一系列散发性肾癌中，发现了获得性TRC 8突变。与贴片类似，TRC 8可能充当信号受体，而其他待定义的途径成员是涉及肾脏和甲状腺的恶性疾病的突变候选者。
The 3;8 chromosomal translocation, t(3;8) (p14.2;q24.1), was described in a family with classical features of hereditary renal cell carcinoma,]Previous studies demonstrated that the 3p14.2 breakpoint interrupts the fragile histidine triad gene (FHIT) in its 5' noncoding region. However, evidence that FHIT is causally related to renal or other malignancies is controversial. We now show that the 8q24.1 breakpoint region encodes a 664-aa multiple membrane spanning protein, TRC8, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular loop that participates in the binding of sonic hedgehog, In the 3;8 translocation, TRC8 is fused to FHIT and is disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. In a series of sporadic renal carcinomas, an acquired TRC8 mutation was identified. By analogy to patched, TRC8 might function as a signaling receptor and other pathway members, to be defined, are mutation candidates in malignant diseases involving the kidney and thyroid.