Bianco Julia Raffaella, Li YiJing, Petranyi Agota, Fabian Zsolt
School of Medicine and Dentistry, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
Centre of Excellence for Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary.
Int J Mol Sci. 2024 Dec 21;25(24):13693. doi: 10.3390/ijms252413693.
Cancer is among the leading causes of mortality in developed countries due to limited available therapeutic modalities and high rate of morbidity. Although malignancies might show individual genetic landscapes, recurring aberrations in the neoplastic genome have been identified in the wide range of transformed cells. These include translocations of frequently affected loci of the human genetic material like the Ewing sarcoma breakpoint region 1 () of chromosome 22 that results in malignancies with mesodermal origin. These cytogenetic defects frequently result in the genesis of fusion genes involving and a number of genes from partner loci. One of these chromosomal rearrangements is the reciprocal translocation between the q13 and q12 loci of chromosome 12 and 22, respectively, that is believed to initiate cancer formation by the genesis of a novel, chimeric transcription factor provoking dysregulated gene expression. Since soft-tissue neoplasms carrying t(12;22)(q13;q12) have very poor prognosis and clinical modalities specifically targeting t(12;22)(q13;q12)-harboring cells are not available to date, understanding this DNA aberration is not only timely but urgent. Here, we review our current knowledge of human malignancies carrying the specific subset of rearrangements that leads to the expression of the EWSR1::ATF1 tumor-driver chimeric protein.
由于可用的治疗方式有限且发病率高，癌症是发达国家主要的死亡原因之一。尽管恶性肿瘤可能表现出个体的基因图谱，但在广泛的转化细胞中已发现肿瘤基因组中存在反复出现的畸变。这些包括人类遗传物质中频繁受影响位点的易位，如22号染色体上的尤因肉瘤断点区域1（EWSR1），其导致中胚层起源的恶性肿瘤。这些细胞遗传学缺陷经常导致融合基因的产生，涉及EWSR1和来自伙伴位点的许多基因。其中一种染色体重排是12号和22号染色体的q13和q12位点之间的相互易位，据信这种易位通过产生一种新的嵌合转录因子引发基因表达失调，从而启动癌症形成。由于携带t(12;22)(q13;q12)的软组织肿瘤预后很差，且迄今为止尚无专门针对携带t(12;22)(q13;q12)细胞的临床治疗方法，了解这种DNA畸变不仅及时而且紧迫。在这里，我们回顾了目前关于携带特定EWSR1重排子集的人类恶性肿瘤的知识，这些重排导致EWSR1::ATF1肿瘤驱动嵌合蛋白的表达。
