研究动态
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KIF14和MDM4/PI3KC2β等位基因的复制计时异常以及染色体非整倍体作为发生染色体不稳定性和治疗反应差的恶性家族性肿瘤患者的标记。

Replication Timing Aberration of KIF14 and MDM4 / PI3KC 2 β Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients.

发表日期:2023 Jun
作者: Fernanda Rocha Rojas Ayala, Jeffrey William Martin, Carmen Silvia Bertuzzo
来源: Epigenetics & Chromatin

摘要:

等位基因对的复制时间严格按照表达、基因组稳定性和表观遗传变化进行调节,肿瘤发生可能与各种肿瘤中等位基因复制的改变有关。我们的目的是确定这种改变在尤文氏肉瘤(EFT)患者中是否具有预后价值。使用KIF14和MDM4/PI3KC 2β以及第8和第12号染色体的着丝粒卫星序列进行复制时间评估。通过计数第8和第12号染色体的拷贝数来评估非整倍体性。采用多色荧光原位杂交技术在135例EFT中细胞遗传学上检测复制时间和非整倍体性。三体性8号染色体的患者呈现MDM4/PI3KC 2β基因的异步复制模式(SD)的相关性(P=0.013)。三体性12号染色体与KIF14探针信号同步模式(DD)相关(P=0.04)。 KIF14的DD同步复制模式与年龄呈相关性(P<0.0001),相同位点的SS同步复制模式与肺转移呈相关性(P=0.012)。呈现MDM4/PI3KC 2β多重信号的患者亚组与治疗反应(P=0.045)和年龄(P=0.033)呈相关性。 KIF14的复制模式可能与染色体不稳定有显着关联,而MDM4/PI3KC 2β可能是EFT患者不良治疗反应的相当新的标记。作者(S)。这是由Thieme出版的开放获取文章,根据创作共享署名许可证发布,只要原作品得到正确引用,就可以不受限制地使用、分发和复制。 (https://creativecommons.org/licenses/by/4.0/)。
Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The KIF14 and MDM4 / PI3KC 2β and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments. Aneuploidy was assessed by enumerating the copy numbers of chromosomes 8 and 12. Replication timing and aneuploidy were detected cytogenetically using multicolors fluorescence in situ hybridization assay applied in 135 EFT. Patients with trisomy 8 presented an association with an asynchronous replication pattern (SD) of MDM4 / PI3KC 2β genes ( p  = 0.013). Trisomy 12 was associated with a synchronous pattern (DD) of KIF14 probe signals ( p  = 0.04). The DD synchronous replication pattern of KIF14 showed a correlation with age ( p  < 0.0001), and the SS synchronous replication pattern of the same locus showed a correlation with lung metastatic ( p  = 0.012). The subgroup of patients presenting with multiplet signals of MDM4 / PI3KC 2β showed an association with treatment response ( p  = 0.045) and age ( p  = 0.033). Replication pattern of KIF14 may, significantly, be associated with chromosomal instability as MDM4 / PI3KC 2β may be a considerably new marker of poor treatment response in EFT patients.The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).