Greco A, Miranda C, Pagliardini S, Fusetti L, Bongarzone I, Pierotti M A
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Genes Chromosomes Cancer. 1997 Jun;19(2):112-23.
The NTRK1 gene in the q arm of chromosome 1 encodes one of the receptors for the nerve growth factor and is frequently activated as an oncogene in papillary thyroid carcinomas. The activation is due to chromosomal rearrangements juxtaposing the NTRK1 tyrosine kinase domain to 5'-end sequences from different genes. The thyroid TRK oncogenes are activated by recombination with at least three different genes: the gene coding for tropomyosin and TPR, both on chromosome 1,and TFG on chromosome 3. In a previous study, we showed that two tumors carrying the TPR/NTRK1 rearrangement contained structurally different oncogenes named TRK-T1 and TRK-T2. In this paper, we report (1) the cDNA structure of TRK-T2, (2) evidence that TRK-T2 is generated by different rearrangements in two thyroid tumors, and (3) a detailed analysis of the three different TPR/NTRK1 rearrangements. With molecular studies based on Southern blot hybridization, cloning, and sequencing, we show that all the rearrangements are nearly balanced, involving deletion, insertion, or duplication of only few nucleotides. In one case, an additional rearrangement involving sequences derived from chromosome 17 was detected.
位于1号染色体长臂q臂上的NTRK1基因编码神经生长因子的一种受体，在甲状腺乳头状癌中常作为癌基因被激活。这种激活是由于染色体重排，使NTRK1酪氨酸激酶结构域与来自不同基因的5'端序列并列。甲状腺TRK癌基因通过与至少三种不同基因重组而被激活：编码原肌球蛋白的基因和TPR基因，二者均位于1号染色体上，以及位于3号染色体上的TFG基因。在先前的一项研究中，我们发现两个携带TPR/NTRK1重排的肿瘤含有结构不同的癌基因，分别命名为TRK-T1和TRK-T2。在本文中，我们报告了（1）TRK-T2的cDNA结构，（2）TRK-T2由两个甲状腺肿瘤中不同重排产生的证据，以及（3）对三种不同的TPR/NTRK1重排的详细分析。通过基于Southern印迹杂交、克隆和测序的分子研究，我们表明所有重排几乎都是平衡的，仅涉及少数核苷酸的缺失、插入或重复。在一个病例中，检测到了另一种涉及来自17号染色体序列的重排。
