Distinct DNA methylation patterns associated with treatment resistance in metastatic castration resistant prostate cancer.

Antineoplastic Agents / pharmacology Benzamides / pharmacology Biomarkers, Tumor Circulating Tumor DNA CpG Islands DNA Methylation Drug Resistance, Neoplasm / genetics Epigenesis, Genetic Gene Expression Regulation, Neoplastic Humans Male Nitriles / pharmacology Phenylthiohydantoin / pharmacology Promoter Regions, Genetic Prostatic Neoplasms, Castration-Resistant / drug therapy

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 03 2021
Historique:
received: 20 10 2020
accepted: 02 03 2021
entrez: 24 3 2021
pubmed: 25 3 2021
medline: 31 1 2023
Statut: epublish

Résumé

Androgens are a major driver of prostate cancer (PCa) and continue to be a critical treatment target for advanced disease, which includes castration therapy and antiandrogens. However, resistance to these therapies leading to metastatic castration-resistant prostate cancer (mCRPC), and the emergence of treatment-induced neuroendocrine disease (tNEPC) remains an ongoing challenge. Instability of the DNA methylome is well established as a major hallmark of PCa development and progression. Therefore, investigating the dynamics of the methylation changes going from the castration sensitive to the tNEPC state would provide insights into novel mechanisms of resistance. Using an established xenograft model of CRPC, genome-wide methylation analysis was performed on cell lines representing various stages of PCa progression. We confirmed extensive methylation changes with the development of CRPC and tNEPC using this model. This included key genes and pathways associated with cellular differentiation and neurodevelopment. Combined analysis of methylation and gene expression changes further highlighted genes that could potentially serve as therapeutic targets. Furthermore, tNEPC-related methylation signals from this model were detectable in circulating cell free DNA (cfDNA) from mCRPC patients undergoing androgen-targeting therapies and were associated with a faster time to clinical progression. These potential biomarkers could help with identifying patients with aggressive disease.

Identifiants

DOI: 10.1038/s41598-021-85812-3 PMID: 33758253 PMC: PMC7988053
pubmed: 33758253
doi: 10.1038/s41598-021-85812-3
pii: 10.1038/s41598-021-85812-3
pmc: PMC7988053
doi:

Substances chimiques

Antineoplastic Agents 0
Benzamides 0
Biomarkers, Tumor 0
Circulating Tumor DNA 0
Nitriles 0
Phenylthiohydantoin 2010-15-3
enzalutamide 93T0T9GKNU

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6630

Références

Wong, Y. N., Ferraldeschi, R., Attard, G. & de Bono, J. Evolution of androgen receptor targeted therapy for advanced prostate cancer. Nat. Rev. Clin. Oncol. 11, 365–376 (2014).
pubmed: 24840076 doi: 10.1038/nrclinonc.2014.72
Sridhar, S. S. et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment. Eur. Urol. 65, 289–299 (2014).
doi: 10.1016/j.eururo.2013.08.008 pubmed: 23957948
Crawford, E. D., Petrylak, D. & Sartor, O. Navigating the evolving therapeutic landscape in advanced prostate cancer. Urol. Oncol. 35S, S1–S13 (2017).
pubmed: 28283376 doi: 10.1016/j.urolonc.2017.01.020
Dai, C., Heemers, H. & Sharifi, N. Androgen signaling in prostate cancer. Cold Spring Harb. Perspect. Med. 7, a030452 (2017).
pubmed: 28389515 pmcid: 5580512 doi: 10.1101/cshperspect.a030452
Scher, H. I. et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med. 367, 1187–1197 (2012).
pubmed: 22894553 doi: 10.1056/NEJMoa1207506
Loriot, Y. et al. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 16, 509–521 (2015).
pubmed: 25888263 doi: 10.1016/S1470-2045(15)70113-0
de Bono, J. S. et al. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 364, 1995–2005 (2011).
pubmed: 21612468 pmcid: 3471149 doi: 10.1056/NEJMoa1014618
Ryan, C. J. et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 16, 152–160 (2015).
pubmed: 25601341 doi: 10.1016/S1470-2045(14)71205-7
Saad, F. et al. 2019 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) guideline: management of castration-resistant prostate cancer (CRPC). Can. Urol. Assoc. J. 13, 307–314 (2019).
pubmed: 31603409 pmcid: 6788916 doi: 10.5489/cuaj.6136
So, A. I. et al. Canadian Urological Association-Canadian Urologic Oncology Group guideline on metastatic castration-naive and castration-sensitive prostate cancer. Can. Urol. Assoc. J. 14, 17–23 (2020).
pubmed: 31999544
Armenia, J. et al. The long tail of oncogenic drivers in prostate cancer. Nat. Genet. 50, 645–651 (2018).
pubmed: 29610475 pmcid: 6107367 doi: 10.1038/s41588-018-0078-z
Bluemn, E. G. et al. Androgen receptor pathway-independent prostate cancer is sustained through FGF signaling. Cancer Cell 32, 474e476-489e476 (2017).
doi: 10.1016/j.ccell.2017.09.003
Aggarwal, R. et al. Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study. J. Clin. Oncol. 36, 2492–2503 (2018).
pubmed: 29985747 pmcid: 6366813 doi: 10.1200/JCO.2017.77.6880
Gonzalez-Billalabeitia, E., Conteduca, V., Wetterskog, D., Jayaram, A. & Attard, G. Circulating tumor DNA in advanced prostate cancer: transitioning from discovery to a clinically implemented test. Prostate Cancer Prostatic Dis. 22, 195–205 (2019).
pubmed: 30413805 doi: 10.1038/s41391-018-0098-x
Robinson, D. et al. Integrative clinical genomics of advanced prostate cancer. Cell 162, 454 (2015).
pubmed: 28843286 doi: 10.1016/j.cell.2015.06.053
Yegnasubramanian, S. Prostate cancer epigenetics and its clinical implications. Asian J. Androl. 18, 549–558 (2016).
pubmed: 27212125 pmcid: 4955178 doi: 10.4103/1008-682X.179859
Massie, C. E., Mills, I. G. & Lynch, A. G. The importance of DNA methylation in prostate cancer development. J. Steroid Biochem. Mol. Biol. 166, 1–15 (2017).
pubmed: 27117390 doi: 10.1016/j.jsbmb.2016.04.009
Brocks, D. et al. Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer. Cell Rep. 8, 798–806 (2014).
pubmed: 25066126 doi: 10.1016/j.celrep.2014.06.053
Aryee, M. J. et al. DNA methylation alterations exhibit intraindividual stability and interindividual heterogeneity in prostate cancer metastases. Sci. Transl. Med. 5, 169ra110 (2013).
doi: 10.1126/scitranslmed.3005211
Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat. Med. 22, 298–305 (2016).
pubmed: 26855148 pmcid: 4777652 doi: 10.1038/nm.4045
Puca, L., Vlachostergios, P. J. & Beltran, H. Neuroendocrine Differentiation in Prostate Cancer: Emerging Biology, Models, and Therapies (Cold Spring Harb. Perspect, 2018).
Davies, A., Zoubeidi, A. & Selth, L. A. The epigenetic and transcriptional landscape of neuroendocrine prostate cancer. Endocr. Relat. Cancer 27, R35–R50 (2020).
pubmed: 31804971 doi: 10.1530/ERC-19-0420
Dardenne, E. et al. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell 30, 563–577 (2016).
pubmed: 27728805 pmcid: 5540451 doi: 10.1016/j.ccell.2016.09.005
Kuruma, H. et al. A novel antiandrogen, compound 30, suppresses castration-resistant and MDV3100-resistant prostate cancer growth in vitro and in vivo. Mol. Cancer Ther. 12, 567–576 (2013).
pubmed: 23493310 doi: 10.1158/1535-7163.MCT-12-0798
Matsumoto, H. et al. Cotargeting androgen receptor and clusterin delays castrate-resistant prostate cancer progression by inhibiting adaptive stress response and AR stability. Cancer Res. 73, 5206–5217 (2013).
pubmed: 23786771 doi: 10.1158/0008-5472.CAN-13-0359
Zelic, R. et al. Global DNA hypomethylation in prostate cancer development and progression: a systematic review. Prostate Cancer Prostatic Dis. 18, 1–12 (2015).
pubmed: 25384337 doi: 10.1038/pcan.2014.45
Zhao, S. G. et al. The DNA methylation landscape of advanced prostate cancer. Nat. Genet. 52, 778–789 (2020).
pubmed: 32661416 pmcid: 7454228 doi: 10.1038/s41588-020-0648-8
Hwang, J. H. et al. CREB5 promotes resistance to androgen-receptor antagonists and androgen deprivation in prostate cancer. Cell Rep. 29, 2355e2356-2370e2356 (2019).
doi: 10.1016/j.celrep.2019.10.068
Cancer Genome Atlas Research N. The molecular taxonomy of primary prostate cancer. Cell 163, 1011–1025 (2015).
doi: 10.1016/j.cell.2015.10.025
Fanjul-Fernandez, M. et al. Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas. Nat. Commun. 4, 2531 (2013).
pubmed: 24100690 doi: 10.1038/ncomms3531
Simovic, I., Castano-Rodriguez, N. & Kaakoush, N. O. OPCML: a promising biomarker and therapeutic avenue. Trends Cancer 5, 463–466 (2019).
pubmed: 31421903 doi: 10.1016/j.trecan.2019.06.002
Oksenberg, N. & Ahituv, N. The role of AUTS2 in neurodevelopment and human evolution. Trends Genet. 29, 600–608 (2013).
pubmed: 24008202 doi: 10.1016/j.tig.2013.08.001
Llamosas, N. et al. SYNGAP1 controls the maturation of dendrites, synaptic function, and network activity in developing human neurons. J. Neurosci. 40, 7980–7994 (2020).
pubmed: 32887745 doi: 10.1523/JNEUROSCI.1367-20.2020 pmcid: 7548701
Schayek, H. et al. Global methylation analysis identifies PITX2 as an upstream regulator of the androgen receptor and IGF-I receptor genes in prostate cancer. Horm. Metab. Res. 44, 511–519 (2012).
pubmed: 22495974 doi: 10.1055/s-0032-1311566
Gara, R. K. et al. Slit/robo pathway: a promising therapeutic target for cancer. Drug Discov. Today 20, 156–164 (2015).
pubmed: 25245168 doi: 10.1016/j.drudis.2014.09.008
Beltran, H. et al. Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. J. Clin. Invest. 130, 1653–1668 (2020).
pubmed: 32091413 pmcid: 7108892 doi: 10.1172/JCI131041
Baylin, S. B. & Jones, P. A. Epigenetic determinants of cancer. Cold Spring Harb. Perspect. Biol. 8, a019505 (2016).
pubmed: 27194046 pmcid: 5008069 doi: 10.1101/cshperspect.a019505
Bishop, J. L. et al. The master neural transcription factor BRN2 is an androgen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov. 7, 54–71 (2017).
pubmed: 27784708 doi: 10.1158/2159-8290.CD-15-1263
Sharma, N. L. et al. The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man. Cancer Cell 23, 35–47 (2013).
pubmed: 23260764 doi: 10.1016/j.ccr.2012.11.010
Lee, G. T. et al. WNT5A induces castration-resistant prostate cancer via CCL2 and tumour-infiltrating macrophages. Br. J. Cancer 118, 670–678 (2018).
pubmed: 29381686 pmcid: 5846063 doi: 10.1038/bjc.2017.451
Yamamoto, H. et al. Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase. Oncogene 29, 2036–2046 (2010).
pubmed: 20101234 doi: 10.1038/onc.2009.496
Sharma, A. et al. The prostate metastasis suppressor gene NDRG1 differentially regulates cell motility and invasion. Mol. Oncol. 11, 655–669 (2017).
pubmed: 28371345 pmcid: 5467496 doi: 10.1002/1878-0261.12059
Hsu, C. M. et al. Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment. Oncotarget 8, 74348–74358 (2017).
pubmed: 29088791 pmcid: 5650346 doi: 10.18632/oncotarget.20637
Leon, K. et al. Structural basis for adhesion G protein-coupled receptor Gpr126 function. Nat. Commun. 11, 194 (2020).
pubmed: 31924782 pmcid: 6954182 doi: 10.1038/s41467-019-14040-1
Wang, W. Y. et al. Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway. Cancer Cell Int. 19, 86 (2019).
pubmed: 30996686 pmcid: 6451308 doi: 10.1186/s12935-019-0780-7
Chen, D., Bhat-Nakshatri, P., Goswami, C., Badve, S. & Nakshatri, H. ANTXR1, a stem cell-enriched functional biomarker, connects collagen signaling to cancer stem-like cells and metastasis in breast cancer. Cancer Res. 73, 5821–5833 (2013).
pubmed: 23832666 pmcid: 3778138 doi: 10.1158/0008-5472.CAN-13-1080
Fan, L. et al. CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion. Oncotarget 8, 53244–53261 (2017).
pubmed: 28881808 pmcid: 5581107 doi: 10.18632/oncotarget.18387
Owusu-Ansah, K. G. et al. COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer. Int. J. Oncol. 55, 391–404 (2019).
pubmed: 31268154 pmcid: 6615918
Spanjol, J. et al. Role of bone morphogenetic proteins in human prostate cancer pathogenesis and development of bone metastases: immunohistochemical study. Coll. Antropol. 34(Suppl 2), 119–125 (2010).
pubmed: 21302710
Ganguly, S. S. et al. Notch3 promotes prostate cancer-induced bone lesion development via MMP-3. Oncogene 39, 204–218 (2020).
pubmed: 31467432 doi: 10.1038/s41388-019-0977-1
Wang, C. H. et al. Flot2 promotes tumor growth and metastasis through modulating cell cycle and inducing epithelial-mesenchymal transition of hepatocellular carcinoma. Am. J. Cancer Res. 7, 1068–1083 (2017).
pubmed: 28560058 pmcid: 5446475
Yin, X. et al. Protocadherin 17 functions as a tumor suppressor suppressing Wnt/beta-catenin signaling and cell metastasis and is frequently methylated in breast cancer. Oncotarget 7, 51720–51732 (2016).
pubmed: 27351130 pmcid: 5239510 doi: 10.18632/oncotarget.10102
Kim, S. et al. PEG10 is associated with treatment-induced neuroendocrine prostate cancer. J. Mol. Endocrinol. 63, 39–49 (2019).
pubmed: 31013476 doi: 10.1530/JME-18-0226
Zhang, P., Schaefer-Klein, J., Cheville, J. C., Vasmatzis, G. & Kovtun, I. V. Frequently rearranged and overexpressed delta-catenin is responsible for low sensitivity of prostate cancer cells to androgen receptor and beta-catenin antagonists. Oncotarget 9, 24428–24442 (2018).
pubmed: 29849951 pmcid: 5966253 doi: 10.18632/oncotarget.25319
Peter, M. R. et al. Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment. Epigenomics 12, 1317–1332 (2020).
pubmed: 32867540 doi: 10.2217/epi-2020-0173
Tina, E. et al. The mitochondrial transporter SLC25A43 is frequently deleted and may influence cell proliferation in HER2-positive breast tumors. BMC Cancer 12, 350 (2012).
pubmed: 22883974 pmcid: 3462703 doi: 10.1186/1471-2407-12-350
Loh, X. Y. et al. RNA-binding protein ZFP36L1 suppresses hypoxia and cell-cycle signaling. Cancer Res. 80, 219–233 (2020).
pubmed: 31551365 doi: 10.1158/0008-5472.CAN-18-2796
Akamatsu, S. et al. The placental gene PEG10 promotes progression of neuroendocrine prostate cancer. Cell Rep. 12, 922–936 (2015).
pubmed: 26235627 doi: 10.1016/j.celrep.2015.07.012
Govaere, O. et al. The PDGFRalpha-laminin B1-keratin 19 cascade drives tumor progression at the invasive front of human hepatocellular carcinoma. Oncogene 36, 6605–6616 (2017).
pubmed: 28783171 pmcid: 5702717 doi: 10.1038/onc.2017.260
Rao, A. & Herr, D. R. G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells. Biochim. Biophys. Acta Mol. Cell Res. 1864, 1318–1327 (2017).
pubmed: 28476646 doi: 10.1016/j.bbamcr.2017.05.001
Labrecque, M. P. et al. Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer. J. Clin. Invest. 129, 4492–4505 (2019).
pubmed: 31361600 pmcid: 6763249 doi: 10.1172/JCI128212
Tian, Y. et al. ChAMP: updated methylation analysis pipeline for Illumina BeadChips. Bioinformatics 33, 3982–3984 (2017).
pubmed: 28961746 pmcid: 5860089 doi: 10.1093/bioinformatics/btx513
Teschendorff, A. E. et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics 29, 189–196 (2013).
pubmed: 23175756 doi: 10.1093/bioinformatics/bts680
Phipson, B., Maksimovic, J. & Oshlack, A. missMethyl: an R package for analyzing data from Illumina’s HumanMethylation450 platform. Bioinformatics 32, 286–288 (2016).
pubmed: 26424855 doi: 10.1093/bioinformatics/btv560
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886 doi: 10.1093/bioinformatics/bts635
Savic, N. et al. Histone chaperone paralogs have redundant, cooperative, and divergent functions in yeast. Genetics 213, 1301–1316 (2019).
pubmed: 31604797 pmcid: 6893378 doi: 10.1534/genetics.119.302235

Auteurs

Madonna R Peter (MR)

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, 60 Murray Street, Toronto, ON, M5T 3L9, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.

Misha Bilenky (M)

Canada's Michael Smith Genome Science Center, BC Cancer Agency, Vancouver, Canada.

Alastair Davies (A)

Vancouver Prostate Centre, Vancouver, BC, Canada.

Ruth Isserlin (R)

Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada.

Gary D Bader (GD)

Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada.

Neil E Fleshner (NE)

Division of Urology, Departments of Surgery and Surgical Oncology, University Health Network, Toronto, Canada.

Martin Hirst (M)

Canada's Michael Smith Genome Science Center, BC Cancer Agency, Vancouver, Canada.
Department of Microbiology and Immunology and Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.

Amina Zoubeidi (A)

Vancouver Prostate Centre, Vancouver, BC, Canada.

Bharati Bapat (B)

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, 60 Murray Street, Toronto, ON, M5T 3L9, Canada. bapat@lunenfeld.ca.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. bapat@lunenfeld.ca.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Benzoates › Benzamides › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN tumoral › ADN tumoral circulant › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Ilots CpG › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Composés chimiques organiques › Nitriles › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Imidazoles › Imidazolidines › Hydantoïnes › Thiohydantoïnes › 3-Phényl-2-thiohydantoïne › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Distinct DNA methylation patterns associated...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Tumeurs prostatiques résistantes à la castration › Distinct DNA methylation patterns associated...