Bounacer A, Schlumberger M, Wicker R, Du-Villard J A, Caillou B, Sarasin A, Suárez H G
Laboratoire de Génétique Moléculaire UPR 42, Institut de Recherches sur le Cancer, CNRS, Villejuif, France.
Br J Cancer. 2000 Jan;82(2):308-14. doi: 10.1054/bjoc.1999.0920.
Rearrangements of NTRK1 proto-oncogene were detected in 'spontaneous' papillary thyroid carcinomas with a frequency varying from 5 to 25% in different studies. These rearrangements result in the formation of chimaeric genes composed of the tyrosine kinase domain of NTRK1 fused to 5' sequences of different genes. To investigate if the NTRK1 gene plays a role in radiation-induced thyroid carcinogenesis, we looked for the presence of NTRK1-activating rearrangements in 32 human thyroid tumours (16 follicular adenomas, 14 papillary carcinomas and two lymph-node metastases of papillary thyroid carcinomas) from patients who had received external radiation, using the reverse transcription polymerase chain reaction, Southern blot and direct sequencing techniques. These data were compared with those obtained in a series of 28 'spontaneous' benign and malignant thyroid tumours, collected from patients without a history of radiation exposure and four in vitro culture cell lines derived from 'spontaneous' thyroid cancers. Our results concerning the radiation-associated tumours showed that only rearrangements between NTRK1 and TPM3 genes (TRK oncogene) were detected in 2/14 papillary carcinomas and in one lymph-node metastasis of one of these papillary thyroid carcinomas. All the radiation-associated adenomas were negative. In the 'spontaneous' tumours, only one of the 14 papillary carcinomas and one of the four in vitro culture cell lines, derived from a papillary carcinoma, presented a NTRK1 rearrangement also with the TPM3 gene. Twenty-five of this series of radiation-associated tumours were previously studied for the ras and RET/PTC oncogenes. In conclusion, our data: (a) show that the overall frequency of NTRK1 rearrangements is similar between radiation-associated (2/31: 6%) and 'spontaneous' epithelial thyroid tumours (2/32: 6%). The frequency, if we consider exclusively the papillary carcinomas, is in both cases 12%; (b) show that the TRK oncogene plays a role in the development of a minority of radiation-associated papillary thyroid carcinomas but not in adenomas; and (c) confirm that RET/PTC rearrangements are the major genetic alteration associated with ionizing radiation-induced thyroid tumorigenesis.
在“自发”的甲状腺乳头状癌中检测到NTRK1原癌基因重排，不同研究中其频率在5%至25%之间变化。这些重排导致嵌合基因的形成，该嵌合基因由NTRK1的酪氨酸激酶结构域与不同基因的5'序列融合而成。为了研究NTRK1基因在辐射诱导的甲状腺癌发生中是否起作用，我们使用逆转录聚合酶链反应、Southern印迹和直接测序技术，在32例接受过外照射的患者的人甲状腺肿瘤（16例滤泡性腺瘤、14例乳头状癌和2例甲状腺乳头状癌的淋巴结转移灶）中寻找NTRK1激活重排的存在。将这些数据与从无辐射暴露史的患者收集的28例“自发”的良性和恶性甲状腺肿瘤以及4种源自“自发”甲状腺癌的体外培养细胞系中获得的数据进行比较。我们关于辐射相关肿瘤的结果表明，仅在2/14例乳头状癌和其中1例甲状腺乳头状癌的1个淋巴结转移灶中检测到NTRK1与TPM3基因（TRK癌基因）之间的重排。所有辐射相关的腺瘤均为阴性。在“自发”肿瘤中，14例乳头状癌中的1例以及4种源自乳头状癌的体外培养细胞系中的1例也出现了与TPM3基因的NTRK1重排。该系列辐射相关肿瘤中有25例之前研究过ras和RET/PTC癌基因。总之，我们的数据：(a)表明辐射相关（2/31: 6%）和“自发”上皮性甲状腺肿瘤（2/32: 6%）中NTRK1重排的总体频率相似。如果仅考虑乳头状癌，两种情况下的频率均为12%；(b)表明TRK癌基因在少数辐射相关的甲状腺乳头状癌的发生中起作用，但在腺瘤中不起作用；(c)证实RET/PTC重排是与电离辐射诱导的甲状腺肿瘤发生相关的主要基因改变。
