Genes Controlled by DNA Methylation Are Involved in Wilms Tumor Progression
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Collection and DNA and RNA Extraction
2.2. Infinium HumanMethylation450 BeadChip Arrays (Illumina) Procedures
2.3. Methylation Statistical Analysis
2.4. RNA Library Construction and Sequencing
2.5. Gene Expression Analysis
3. Results
3.1. DNA Variability Suggests the Existence of Two Groups of Metastatic Tissues
3.2. Methylation Differences May Be Related to DNMTs and TETs Expression
3.3. Genes Controlled by DNA Methylation Confirm the Existence of Two Groups of Metastases
3.4. Characterization of the DMRs within the Metastatic Groups
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample (ID) | Age at Diagnosis (years) | Gender | Histology (Primary Tumor) | Patient Stage | Relapse Site | Histology (Metastasis) | Technique |
---|---|---|---|---|---|---|---|
1 | 3 | F | Blastemal | III | Left lung | Mixed | RNA-Seq/450k |
2 | 7 | M | Regressive | II | Left lung | Epithelial | RNA-Seq/450k |
3 | 5 | M | Mixed | I | Left lung | Blastemal | RNA-Seq/450k |
4 | 3 | F | Mixed | II | Right lung | Blastemal | RNA-Seq |
5 | 3 | F | Mixed | II | Right and left lung | Epithelial | 450k |
6 | 9 | M | Mixed | I | Left lung | Mixed | 450k |
7 | 4 | M | Regressive | I | Right lung | Blastemal | RNA-Seq |
9 | 3 | M | Mixed | I | Right lung | Blastemal | RNA-Seq/450k |
10 | 6 | M | Mixed | I | Right lung | Mixed | RNA-Seq/450k |
Gene | DMR Location | Number of CpGs | DMR Width (Bp) | Minimum p-value | Methylation Status (MaxBetaFC) | Methylation Status (MeanBetaFC) | Expression (Log2FC) |
---|---|---|---|---|---|---|---|
ACCS | chr11:44087396-44088257 | 12 | 862 | 5 × 10−19 | 0.5 | 0.3 | −1.4 |
AQP1 | chr7:30951064-30951801 | 11 | 738 | 6 × 10−18 | 0.4 | 0.1 | −3.9 |
BHMT | chr5:78407153-78407683 | 8 | 531 | 4 × 10−40 | 0.5 | 0.4 | −7.5 |
BRCA1 | chr17:41277974-41279022 | 21 | 1049 | 2 × 10−25 | −0.5 | −0.2 | 2.2 |
CD81 | chr11:2397255-2398336 | 21 | 1082 | 2 × 10−46 | 0.4 | 0.2 | −1.2 |
CIDEB | chr14:24779793-24780926 | 13 | 1134 | 4 × 10−43 | 0.6 | 0.2 | −2.2 |
CLDN10 | chr13:96204518-96204978 | 8 | 461 | 1 × 10−4 | 0.2 | 0.1 | −5.6 |
CLIC6 | chr21:36041334-36041699 | 8 | 366 | 1 × 10−52 | 0.6 | 0.5 | −3.0 |
CRB3 | chr19:6463949-6464275 | 9 | 327 | 1 × 10−23 | 0.4 | 0.3 | −5.3 |
ELF3 | chr1:201979478-201979938 | 7 | 461 | 1 × 10−6 | 0.3 | 0.1 | −4.8 |
GRHL2 | chr8:102504447-102504859 | 8 | 413 | 7 × 10−16 | 0.3 | 0.2 | −4.0 |
H19 | chr11:2019452-2020560 | 29 | 1109 | 4 × 10−12 | 0.3 | 0.1 | −2.1 |
HLA-A | chr6:29910411-29911095 | 8 | 685 | 4 × 10−18 | 0.4 | 0.2 | −2.2 |
HNF1A | chr12:121416315-121416796 | 7 | 482 | 7 × 10−10 | 0.4 | 0.2 | −4.9 |
HNF4A | chr20:42983920-42984878 | 12 | 959 | 1 × 10−17 | 0.4 | 0.2 | −5.4 |
HOXA-AS3 | chr7:27183816-27185512 | 26 | 1697 | 5 × 10−16 | −0.3 | −0.2 | 2.6 |
HOXA5 | chr7:27183816-27185512 | 26 | 1697 | 5 × 10−16 | −0.3 | −0.2 | 1.8 |
HOXA6 | chr7:27183816-27185512 | 26 | 1697 | 5 × 10−16 | −0.3 | −0.2 | 2.3 |
HOXB-AS3 | chr17:46669455-46670029 | 9 | 575 | 4 × 10−16 | −0.3 | −0.1 | 2.7 |
HSPA2 | chr14:65006688-65007437 | 16 | 750 | 1 × 10−15 | 0.4 | 0.2 | −3.9 |
IRF6 | chr1:209979111-209979779 | 9 | 669 | 3 × 10−22 | 0.5 | 0.3 | −2.8 |
KRT7 | chr12:52626814-52627576 | 8 | 763 | 1 × 10−8 | 0.4 | 0.2 | −5.8 |
LTF | chr3:46506104-46506554 | 9 | 451 | 3 × 10−5 | 0.3 | 0.2 | −7.0 |
MEST | chr7:130130753-130131730 | 13 | 978 | 3 × 10−9 | −0.2 | −0.1 | 3.7 |
MYO15B | chr17:73583839-73584360 | 9 | 522 | 1 × 10−7 | 0.3 | 0.2 | −1.6 |
PAH | chr12:103310839-103311761 | 9 | 923 | 8 × 10−20 | 0.3 | 0.2 | −8.1 |
PDZK1IP1 | chr1:47655599-47656423 | 7 | 825 | 7 × 10−7 | 0.3 | 0.2 | −7.3 |
POU5F1 | chr6:31148404-31148748 | 7 | 345 | 1 × 10−6 | 0.2 | 0.1 | −4.7 |
PRRG4 | chr11:32851087-32851531 | 9 | 445 | 1 × 10−4 | 0.2 | 0.1 | −4.2 |
RGMA | chr15:93616894-93617168 | 11 | 275 | 2 × 10−9 | −0.3 | −0.2 | 2.7 |
SLC22A18 | chr11:2925594-2925969 | 8 | 376 | 2 × 10−4 | 0.2 | 0.1 | −2.5 |
SLC22A2 | chr6:160679391-160680162 | 10 | 772 | 3 × 10−13 | 0.3 | 0.2 | −8.0 |
SLC25A23 | chr19:6463949-6464275 | 9 | 327 | 1 × 10−23 | 0.4 | 0.3 | −1.6 |
SLC44A4 | chr6:31846769-31847028 | 8 | 260 | 1 × 10−7 | 0.2 | 0.2 | −4.1 |
SLFN12 | chr17:33759512-33760527 | 11 | 1016 | 1 × 10−14 | 0.5 | 0.3 | −1.7 |
SOD3 | chr4:24796689-24797176 | 7 | 488 | 1 × 10−3 | 0.2 | 0.1 | −2.3 |
STRA6 | chr15:74494781-74495354 | 7 | 574 | 4 × 10−15 | −0.3 | −0.2 | 3.6 |
SUSD2 | chr22:24577223-24577448 | 7 | 226 | 4 × 10−3 | 0.3 | 0.1 | −2.7 |
TCIRG1 | chr11:67806118-67806668 | 7 | 551 | 3 × 10−30 | 0.6 | 0.4 | −2.2 |
TMEM140 | chr7:134832544-134833299 | 7 | 756 | 9 × 10−10 | 0.4 | 0.2 | −3.1 |
TNFRSF10A | chr8:23082634-23082961 | 7 | 328 | 2 × 10−4 | 0.3 | 0.2 | −3.1 |
TTC22 | chr1:55266296-55267152 | 8 | 857 | 1 × 10−7 | 0.3 | 0.2 | −5.7 |
UPB1 | chr22:24891141-24891666 | 8 | 526 | 2 × 10−10 | 0.3 | 0.2 | −3.1 |
VWA7 | chr6:31740805-31741184 | 8 | 380 | 1 × 10−9 | 0.2 | 0.2 | −1.7 |
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Guerra, J.V.d.S.; Pereira, B.M.d.S.; Cruz, J.G.V.d.; Scherer, N.d.M.; Furtado, C.; Montalvão de Azevedo, R.; Oliveira, P.S.L.d.; Faria, P.; Boroni, M.; de Camargo, B.; et al. Genes Controlled by DNA Methylation Are Involved in Wilms Tumor Progression. Cells 2019, 8, 921. https://doi.org/10.3390/cells8080921
Guerra JVdS, Pereira BMdS, Cruz JGVd, Scherer NdM, Furtado C, Montalvão de Azevedo R, Oliveira PSLd, Faria P, Boroni M, de Camargo B, et al. Genes Controlled by DNA Methylation Are Involved in Wilms Tumor Progression. Cells. 2019; 8(8):921. https://doi.org/10.3390/cells8080921
Chicago/Turabian StyleGuerra, João Victor da Silva, Bruna Maria de Sá Pereira, Jéssica Gonçalves Vieira da Cruz, Nicole de Miranda Scherer, Carolina Furtado, Rafaela Montalvão de Azevedo, Paulo Sergio Lopes de Oliveira, Paulo Faria, Mariana Boroni, Beatriz de Camargo, and et al. 2019. "Genes Controlled by DNA Methylation Are Involved in Wilms Tumor Progression" Cells 8, no. 8: 921. https://doi.org/10.3390/cells8080921