Prensner John R, Chinnaiyan Arul M
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Curr Opin Genet Dev. 2009 Feb;19(1):82-91. doi: 10.1016/j.gde.2008.11.008. Epub 2009 Feb 21.
New discoveries regarding recurrent chromosomal aberrations in epithelial tumors have challenged the view that gene fusions play a minor role in these cancers. It is now known that recurrent fusions characterize significant subsets of prostate, breast, lung and renal-cell carcinomas, among others. This work has generated new insights into the molecular subtypes of tumors and highlighted important advances in bioinformatics, sequencing, and microarray technology as tools for gene fusion discovery. Given the ubiquity of tyrosine kinases and transcription factors in gene fusions, further interest in the potential 'druggability' of gene fusions with targeted therapeutics has also flourished. Nevertheless, the majority of chromosomal abnormalities in epithelial cancers remain uncharacterized, underscoring the limitations of our knowledge of carcinogenesis and the requirement for further research.
上皮性肿瘤中复发性染色体畸变的新发现挑战了基因融合在这些癌症中作用较小的观点。现在已知复发性融合是前列腺癌、乳腺癌、肺癌和肾细胞癌等重要亚组的特征。这项工作为肿瘤的分子亚型带来了新的见解,并突出了生物信息学、测序和微阵列技术作为基因融合发现工具的重要进展。鉴于酪氨酸激酶和转录因子在基因融合中普遍存在,对基因融合与靶向治疗潜在“可药性”的进一步关注也日益增加。然而,上皮性癌中的大多数染色体异常仍未得到表征,这凸显了我们对致癌作用认识的局限性以及进一步研究的必要性。