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Tytuł pozycji:

Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage

Tytuł:
Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage
Autorzy:
Douglas Meyer
Jacob Kames
Haim Bar
Anton A. Komar
Aikaterini Alexaki
Juan Ibla
Ryan C. Hunt
Luis V. Santana-Quintero
Anton Golikov
Michael DiCuccio
Chava Kimchi-Sarfaty
Temat:
CancerCoCoPUTs
The Cancer Genome Atlas (TCGA)
Cancer transcriptome
Codon usage
Codon pair
Relative synonymous codon usage (RSCU)
Medicine
Genetics
QH426-470
Źródło:
Genome Medicine, Vol 13, Iss 1, Pp 1-18 (2021)
Wydawca:
BMC, 2021.
Rok publikacji:
2021
Kolekcja:
LCC:Medicine
LCC:Genetics
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1756-994X
Relacje:
https://doaj.org/toc/1756-994X
DOI:
10.1186/s13073-021-00935-6
Dostęp URL:
https://doaj.org/article/c7ca96719b204fc496ee0de68b57825b  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.7ca96719b204fc496ee0de68b57825b
Czasopismo naukowe
Abstract Background 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. Methods 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. Results 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. Conclusions 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.

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