Age-, tumor-, and metastatic tissue-associated DNA hypermethylation of a T-box brain 1 locus in human kidney tissue.
Adiposity
/ genetics
Adult
Aged
Aged, 80 and over
Brain
/ metabolism
Brain Neoplasms
/ genetics
Carcinogenesis
/ genetics
Carcinoma, Renal Cell
/ genetics
Cell Line, Tumor
/ metabolism
CpG Islands
/ genetics
DNA Methylation
/ genetics
DNA, Neoplasm
/ genetics
Disease Progression
Epigenesis, Genetic
/ genetics
Female
Humans
Kidney
/ metabolism
Kidney Neoplasms
/ pathology
Male
Middle Aged
RNA, Messenger
/ genetics
Risk Factors
T-Box Domain Proteins
/ genetics
Age
DNA hypermethylation
DNA methylation
Kidney tissue
Metastasis
Metastatic tissue
Tumor progression
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
18 02 2020
18 02 2020
Historique:
received:
25
09
2019
accepted:
03
02
2020
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
3
6
2021
Statut:
epublish
Résumé
While a considerable number of tumor-specific hypermethylated loci have been identified in renal cell cancer (RCC), DNA methylation of loci showing successive increases in normal, tumoral, and metastatic tissues could point to genes with high relevance both for the process of tumor development and progression. Here, we report that DNA methylation of a locus in a genomic region corresponding to the 3'UTR of the transcription factor T-box brain 1 (TBR1) mRNA accumulates in normal renal tissues with age and possibly increased body mass index. Moreover, a further tissue-specific increase of methylation was observed for tumor and metastatic tissue samples. Biometric analyses of the TCGA KIRC methylation data revealed candidate loci for age-dependent and tumor-specific DNA methylation within the last exon and in a genomic region corresponding to the 3'UTR TBR1 mRNA. To evaluate whether methylation of TBR1 shows association with RCC carcinogenesis, we measured 15 tumor cell lines and 907 renal tissue samples including 355 normal tissues, 175 tissue pairs of normal tumor adjacent and corresponding tumor tissue as well 202 metastatic tissues samples of lung, bone, and brain metastases by the use of pyrosequencing. Statistical evaluation demonstrated age-dependent methylation in normal tissue (R = 0.72, p < 2 × 10 Our analyses provide statistical evidence of association between methylation of TBR1 and RCC development and disease progression.
Sections du résumé
BACKGROUND
While a considerable number of tumor-specific hypermethylated loci have been identified in renal cell cancer (RCC), DNA methylation of loci showing successive increases in normal, tumoral, and metastatic tissues could point to genes with high relevance both for the process of tumor development and progression. Here, we report that DNA methylation of a locus in a genomic region corresponding to the 3'UTR of the transcription factor T-box brain 1 (TBR1) mRNA accumulates in normal renal tissues with age and possibly increased body mass index. Moreover, a further tissue-specific increase of methylation was observed for tumor and metastatic tissue samples.
RESULTS
Biometric analyses of the TCGA KIRC methylation data revealed candidate loci for age-dependent and tumor-specific DNA methylation within the last exon and in a genomic region corresponding to the 3'UTR TBR1 mRNA. To evaluate whether methylation of TBR1 shows association with RCC carcinogenesis, we measured 15 tumor cell lines and 907 renal tissue samples including 355 normal tissues, 175 tissue pairs of normal tumor adjacent and corresponding tumor tissue as well 202 metastatic tissues samples of lung, bone, and brain metastases by the use of pyrosequencing. Statistical evaluation demonstrated age-dependent methylation in normal tissue (R = 0.72, p < 2 × 10
CONCLUSIONS
Our analyses provide statistical evidence of association between methylation of TBR1 and RCC development and disease progression.
Identifiants
pubmed: 32070431
doi: 10.1186/s13148-020-0823-x
pii: 10.1186/s13148-020-0823-x
pmc: PMC7029553
doi:
Substances chimiques
DNA, Neoplasm
0
RNA, Messenger
0
T-Box Domain Proteins
0
TBR1 protein, human
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33Références
Cancer Med. 2014 Apr;3(2):300-9
pubmed: 24464810
Epigenetics. 2012 May;7(5):447-57
pubmed: 22419128
Oncogene. 2011 Mar 24;30(12):1390-401
pubmed: 21132003
PLoS One. 2014 Mar 14;9(3):e91440
pubmed: 24633192
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
pubmed: 14681465
Front Neurosci. 2015 Nov 03;9:406
pubmed: 26578866
Nature. 2012 Aug 2;488(7409):100-5
pubmed: 22832583
Hum Mol Genet. 2009 Dec 15;18(24):4808-17
pubmed: 19776032
Carcinogenesis. 2009 Feb;30(2):214-21
pubmed: 19037089
Clin Cancer Res. 2006 Dec 1;12(23):6989-97
pubmed: 17145819
Int J Cancer. 2006 Feb 15;118(4):916-23
pubmed: 16152585
BJU Int. 2012 Jul;110(2 Pt 2):E144-52
pubmed: 22289415
Oncogene. 2003 Jun 26;22(26):4128-33
pubmed: 12821947
Neuro Oncol. 2004 Oct;6(4):281-9
pubmed: 15494095
Br J Cancer. 2013 Jan 15;108(1):131-8
pubmed: 23321515
Front Genet. 2012 May 30;3:94
pubmed: 22666228
J Clin Invest. 2014 Jan;124(1):24-9
pubmed: 24382386
Eur Urol. 2014 Oct;66(4):704-10
pubmed: 24931622
Mol Cancer. 2007 Jul 16;6:49
pubmed: 17634119
PLoS Genet. 2009 Aug;5(8):e1000602
pubmed: 19680444
BMC Cancer. 2007 Jul 23;7:133
pubmed: 17645803
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
Ann Oncol. 2014 Jan;25(1):149-54
pubmed: 24356626
PLoS One. 2010 Dec 30;5(12):e15224
pubmed: 21253009
Forensic Sci Int Genet. 2017 Jul;29:118-125
pubmed: 28419903
Clin Cancer Res. 2006 Sep 1;12(17):5040-6
pubmed: 16951219
PLoS One. 2016 Oct 3;11(10):e0163873
pubmed: 27695045
Nature. 2007 May 24;447(7143):433-40
pubmed: 17522677
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7504-9
pubmed: 11390984
CA Cancer J Clin. 2017 Jan;67(1):7-30
pubmed: 28055103
Oncogene. 2010 Apr 8;29(14):2104-17
pubmed: 20154727
Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2526-32
pubmed: 18086755