Examining transcriptional changes to DNA replication and repair factors over uveal melanoma subtypes.
Examining transcriptional changes to DNA replication and repair factors over uveal melanoma subtypes.
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DOI：
10.1186/s12885-018-4705-y
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发表时间：
2018-08-14
期刊：
影响因子：
3.8
通讯作者：
Kucherlapati M
中科院分区：
文献类型：
--
作者：
Kucherlapati M
不受控制的复制是所有癌症共同的过程，随着肿瘤进展而积累的变化的总和促进了这一过程。这项研究的目的是在转录和基因组水平上检测在复制和修复过程中具有已知生物学特性的小群基因，并将其与葡萄膜黑色素瘤肿瘤进展中的生存相关。已经观察到复制前、启动前和复制体复合体的特定成分、DNA损伤反应和错配修复。对于高于和低于平均改变水平的选定基因，已经产生了两组，并比较了癌症基因组图谱葡萄膜黑色素瘤亚型的表达和存活率。Fisher‘s精确检验表明，3号染色体单体或二体亚型之间的表达存在显著差异。用Log-ranch检验比较了基于疾病特定生存的Kaplan Meier生存分布。有显著变化的基因包括MCM2、MCM4、MCM5、CDC45、MCM10、CIZ1、增殖细胞核抗原、FEN1、LIG1、POLD1、POLE、HUS1、CHECK1、AIPP、MLH3和MSH6。CIZ1基因外显子4跳过以前被认为是一种癌症变异，据报道被用作肺癌的早期血清生物标记物。错配修复蛋白MLH3存在剪接变异，外显子5和外显子7同时缺失。增殖细胞核抗原、FEN1和LIG1的相对表达水平升高，不是由于突变或拷贝数变化。目前的研究提出了复制和修复基因的相对和差异表达的变化，这些基因支持他们的产品与葡萄膜黑色素瘤有因果关系的概念。提出了早期识别生物标记物和治疗方法的具体途径。
Uncontrolled replication is a process common to all cancers facilitated by the summation of changes accumulated as tumors progress. The aim of this study was to examine small groups of genes with known biology in replication and repair at the transcriptional and genomic levels, correlating alterations with survival in uveal melanoma tumor progression. Selected components of Pre-Replication, Pre-Initiation, and Replisome Complexes, DNA Damage Response and Mismatch Repair have been observed. Two groups have been generated for selected genes above and below the average alteration level and compared for expression and survival across The Cancer Genome Atlas uveal melanoma subtypes. Significant differences in expression between subtypes monosomic or disomic for chromosome 3 have been identified by Fisher’s exact test. Kaplan Meier survival distribution based on disease specific survival has been compared by Log-rank test. Genes with significant alteration include MCM2, MCM4, MCM5, CDC45, MCM10, CIZ1, PCNA, FEN1, LIG1, POLD1, POLE, HUS1, CHECK1, ATRIP, MLH3, and MSH6. Exon 4 skipping in CIZ1 previously identified as a cancer variant, and reportedly used as an early serum biomarker in lung cancer was found. Mismatch Repair protein MLH3 was found to have splicing variations with deletions to both Exon 5 and Exon 7 simultaneously. PCNA, FEN1, and LIG1 had increased relative expression levels not due to mutation or to copy number variation. The current study proposes changes in relative and differential expression to replication and repair genes that support the concept their products are causally involved in uveal melanoma. Specific avenues for early biomarker identification and therapeutic approach are suggested.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
7
作者：
Kunnev D;Freeland A;Qin M;Leach RW;Wang J;Shenoy RM;Pruitt SC
通讯作者：
Pruitt SC
影响因子：
8
作者：
Kunnev D;Rusiniak ME;Kudla A;Freeland A;Cady GK;Pruitt SC
通讯作者：
Pruitt SC
影响因子：
16
作者：
Choe KN;Moldovan GL
通讯作者：
Moldovan GL
DOI：
10.2147/opth.s89591
发表时间：
2017
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Krantz BA;Dave N;Komatsubara KM;Marr BP;Carvajal RD
通讯作者：
Carvajal RD