Perner Sven, Wagner Patrick L, Demichelis Francesca, Mehra Rohit, Lafargue Christopher J, Moss Benjamin J, Arbogast Stefanie, Soltermann Alex, Weder Walter, Giordano Thomas J, Beer David G, Rickman David S, Chinnaiyan Arul M, Moch Holger, Rubin Mark A
Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA.
Neoplasia. 2008 Mar;10(3):298-302. doi: 10.1593/neo.07878.
A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently. Because the EML4-ALK fusion was only shown by a reverse transcription-polymerase chain reaction approach, we developed fluorescent in situ hybridization assays to interrogate more than 600 NSCLCs using break-apart probes for EML4 and ALK. We found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that EML4 and/or ALK amplifications also occur. We also observed that, in most cases in which an EML4/ALK alteration is detected, not all of the tumor cells harbor the lesion. By using a detailed multi-fluorescent in situ hybridization probe assay and reverse transcription-polymerase chain reaction, we have evidence that other, more common mechanisms besides gene inversion exist including the possibility of other fusion partners for ALK and EML4. Furthermore, we confirmed the NKX2-1 high-level amplification in a significant subset of NSCLC and found this amplification to be mutually exclusive to ALK and EML4 rearrangements.
最近有独立报道称，在6.7%的非小细胞肺癌（NSCLC）中存在EML4与ALK之间的复发性基因融合，在12%的肺腺癌中存在NKX2-1（TTF1，TITF1）高水平扩增。由于EML4-ALK融合仅通过逆转录-聚合酶链反应方法得以显示，我们开发了荧光原位杂交检测法，使用针对EML4和ALK的分离探针检测600多个NSCLC样本。我们发现，EML4-ALK融合在不到3%的NSCLC样本中出现，并且EML4和/或ALK扩增也会发生。我们还观察到，在大多数检测到EML4/ALK改变的病例中，并非所有肿瘤细胞都存在该病变。通过使用详细的多荧光原位杂交探针检测法和逆转录-聚合酶链反应，我们有证据表明，除了基因倒置外，还存在其他更常见的机制，包括ALK和EML4可能有其他融合伴侣。此外，我们在相当一部分NSCLC中证实了NKX2-1高水平扩增，并发现这种扩增与ALK和EML4重排相互排斥。
