Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

Autor: William G. Nelson, Enrico Munari, Ajay Vaghasia, Michael C. Haffner, George J. Netto, Alcides Chaux, Sarah Karram, Srinivasan Yegnasubramanian, Diana Taheri, Nilda Diana Gonzalez Roibon, Stephania M. Bezerra
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Pathology
Carcinoma Cells
lcsh:Medicine
Renal cell carcinoma
Animal Cells
Medicine and Health Sciences
lcsh:Science
Staining
Cultured Tumor Cells
Aged
80 and over
Multidisciplinary
Cell Staining
Middle Aged
Sertoli cell
Kidney Neoplasms
3. Good health
medicine.anatomical_structure
Oncology
DNA methylation
5-Methylcytosine
Epigenetics
Female
Teratoma
Biological Cultures
Cellular Types
Research Article
Adult
medicine.medical_specialty
Biology
Research and Analysis Methods
Carcinomas
03 medical and health sciences
Cytosine
medicine
Carcinoma
Genetics
Cancer Detection and Diagnosis
Humans
Carcinoma
Renal Cell
Aged
lcsh:R
Renal Cell Carcinoma
Cancer
Cancers and Neoplasms
Biology and Life Sciences
Seminoma
Cell Biology
Cell Cultures
DNA Methylation
medicine.disease
Nuclear Staining
Clear cell renal cell carcinoma
Genitourinary Tract Tumors
030104 developmental biology
Germ Cells
Specimen Preparation and Treatment
lcsh:Q
Urogenital Neoplasms
Zdroj: PLoS ONE, Vol 11, Iss 1, p e0146302 (2016)
PLoS ONE
Popis: Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment.
Databáze: OpenAIRE
Externí odkaz: