Age-, tumor-, and metastatic tissue-associated DNA hypermethylation of a T-box brain 1 locus in human kidney tissue
Posted on 2020-02-19 - 05:16
Abstract 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 × 10−16), association with adiposity (P = 0.019) and tumor-specific hypermethylation (P = 6.1 × 10−19) for RCC tissues. Comparison of tumor and metastatic tissues revealed higher methylation in renal cancer metastases (P = 2.65 × 10−6). Conclusions Our analyses provide statistical evidence of association between methylation of TBR1 and RCC development and disease progression.
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Serth, Jürgen; Peters, Inga; Dubrowinskaja, Natalia; Reese, Christel; Albrecht, Knut; Klintschar, Michael; et al. (2020). Age-, tumor-, and metastatic tissue-associated DNA hypermethylation of a T-box brain 1 locus in human kidney tissue. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4862211.v1
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AUTHORS (13)
JS
Jürgen Serth
IP
Inga Peters
ND
Natalia Dubrowinskaja
CR
Christel Reese
KA
Knut Albrecht
MK
Michael Klintschar
ML
Marcel Lafos
AG
Alexander Grote
AB
Albert Becker
JH
Jörg Hennenlotter
AS
Arnulf Stenzl
HT
Hossein Tezval
MK
Markus Kuczyk