Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.
Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.
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DOI：
10.1186/s13073-021-00935-6
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发表时间：
2021-07-28
期刊：
影响因子：
12.3
通讯作者：
Kimchi-Sarfaty C
中科院分区：
文献类型：
--
作者：
Meyer D;Kames J;Bar H;Komar AA;Alexaki A;Ibla J;Hunt RC;Santana-Quintero LV;Golikov A;DiCuccio M;Kimchi-Sarfaty C
基因表达在多细胞生物的组织中高度可变，影响组织特异性转录组的密码子使用。癌症破坏健康组织的基因表达模式，导致密码子使用偏好改变。密码子使用的主题随着密码子需求的变化而变化，并且癌症中的 tRNA 供应越来越受到人们的关注。我们根据来自 6427 个实体瘤样本和 632 个正常组织样本的癌症基因组图谱 (TCGA) RNA-seq 数据分析了转录组加权密码子和密码子对的使用情况。该数据集代表了影响 11 种不同组织的 32 种癌症类型。我们的分析重点是产生多种实体瘤类型和存在于多种组织中的癌症类型的组织。我们确定了影响同一组织的不同癌症类型的同义密码子使用变化的不同模式。例如，在乳腺浸润性导管癌 (IDC)、浸润性小叶癌 (ILC) 以及混合性浸润性导管和小叶癌 (IDDLC) 中观察到 GGT-甘氨酸显着增加。在 IDC 和 IDLC 中，支持 GGT 的同义密码子偏好的变化与反对 GGC 的同义密码子偏好的变化相关，但在 ILC 中则不然。此外，我们检查了来自同一患者的配对健康/肿瘤组织之间的密码子使用变化。使用 TCGA 的临床数据，我们根据健康和肿瘤特异性密码子使用之间的变化程度对患者进行了生存分析，揭示了较大变化与死亡率增加之间的关联。我们还创建了一个数据库，其中包含源自 TCGA 的癌症特异性密码子和癌症类型的密码子对使用数据，这代表了面向密码子使用的癌症研究的综合工具。根据 TCGA 的数据，我们强调了密码子和密码子对使用的肿瘤类型特异性特征。配对数据揭示了密码子使用模式的可变变化，在设计个性化癌症治疗时必须考虑这一点。相关数据库 CancerCoCoPUTs 代表了癌症中密码子和密码子对使用的综合资源，可在 https://dnahive.fda.gov/review/cancercocoputs/ 上获取。这些发现对于了解癌症状态下 tRNA 供应和密码子需求之间的关系非常重要，并有助于指导新癌症疗法的开发。在线版本包含可在 10.1186/s13073-021-00935-6 获取的补充材料。
Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest. We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues. We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research. Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/. These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics. The online version contains supplementary material available at 10.1186/s13073-021-00935-6.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Gingold, Hila;Tehler, Disa;Pilpel, Yitzhak
通讯作者：
Pilpel, Yitzhak
影响因子：
4
作者：
Hobbs, G. Aaron;Der, Channing J.;Rossman, Kent L.
通讯作者：
Rossman, Kent L.
DOI：
10.1073/pnas.1304227110
发表时间：
2013-08-13
影响因子：
11.1
作者：
Gartner, Jared J.;Parker, Stephen C. J.;Samuels, Yardena
通讯作者：
Samuels, Yardena
影响因子：
3.5
作者：
Griseri, Paola;Bourcier, Christine;Pages, Gilles
通讯作者：
Pages, Gilles