Geurts J M, Schoenmakers E F, Röijer E, Aström A K, Stenman G, van de Ven W J
Center for Human Genetics, University of Leuven & Flanders Interuniversity Institute for Biotechnology, Belgium.
Oncogene. 1998 Feb 19;16(7):865-72. doi: 10.1038/sj.onc.1201609.
Approximately 12% of all pleomorphic adenomas of the salivary glands are characterized by chromosome aberrations involving the chromosome segment 12q13-15. Several chromosomes have been found as translocation partners of chromosome 12, and some of these recurrently. Recently, the HMGIC gene was identified as the target gene affected by the 12q13-15 aberrations. Here, we report the identification and characterization of a new translocation partner gene of HMGIC in pleomorphic adenomas. 3'-RACE analysis of a primary adenoma with an apparently normal karyotype revealed an HMGIC fusion transcript containing ectopic sequences derived from the human NFIB gene, previously mapped to chromosome band 9p24.1. The HMGIC NFIB fusion transcript was also confirmed by RT-PCR. Since the chromosome segment 9p12-24 is repeatedly involved as translocation partner of chromosome 12q13-15 in pleomorphic adenomas, we tested whether NFIB might be a recurrent partner of HMGIC. RT-PCR analysis of a second adenoma with an ins(9;12)(p23;q12q15) as the sole anomaly, revealed that also in this tumor an HMGIC/NFIB hybrid transcript was present. The reciprocal NFIB/HMGIC fusion transcript, however, could not be detected in any of these tumors. Nucleotide sequence analysis of the fusion transcripts indicated that the genetic aberration in both tumors resulted in the replacement of a carboxy-terminal segment of HMGIC by the last five amino acids of NFIB. In conclusion, our results reveal the recurrent involvement of the NFIB gene as translocation partner gene of HMGIC in pleomorphic adenomas.
涎腺多形性腺瘤中约12% 的病例具有涉及染色体12q13 - 15片段的染色体畸变特征。已发现多条染色体作为12号染色体的易位伙伴，其中一些是反复出现的。最近，HMGIC基因被确定为受12q13 - 15畸变影响的靶基因。在此，我们报告了多形性腺瘤中HMGIC一个新的易位伙伴基因的鉴定和特征。对核型明显正常的原发性腺瘤进行3'-RACE分析，发现一个HMGIC融合转录本，其包含来自人NFIB基因的异位序列，该基因先前定位于染色体9p24.1带。RT-PCR也证实了HMGIC NFIB融合转录本的存在。由于在多形性腺瘤中9p12 - 24染色体片段反复作为12q13 - 15染色体的易位伙伴参与其中，我们检测了NFIB是否可能是HMGIC的反复出现的伙伴。对另一例仅存在ins(9;12)(p23;q12q15)这一异常的腺瘤进行RT-PCR分析，结果显示在该肿瘤中也存在HMGIC/NFIB杂交转录本。然而，在任何这些肿瘤中均未检测到相互的NFIB/HMGIC融合转录本。融合转录本的核苷酸序列分析表明，这两个肿瘤中的基因畸变导致HMGIC的羧基末端片段被NFIB的最后五个氨基酸取代。总之，我们的结果揭示了NFIB基因作为HMGIC的易位伙伴基因在多形性腺瘤中反复出现。
