scholarly journals Differentially Methylated Loci Distinguish Ovarian Carcinoma Histological Types: Evaluation of a DNA Methylation Assay in FFPE Tissue

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Linda E. Kelemen ◽  
Martin Köbel ◽  
Angela Chan ◽  
Soreh Taghaddos ◽  
Irina Dinu

Epigenomic markers can identify tumor subtypes, but few platforms can accommodate formalin-fixed paraffin-embedded (FFPE) tumor tissue. We tested different amounts of bisulfite-converted (bs) DNA from six FFPE ovarian carcinomas (OC) of serous, endometrioid, and clear cell histologies and two HapMap constitutional genomes to evaluate the performance of the GoldenGate methylation assay. Methylation status at each 1,505 CpG site was expressed asβ-values. Comparing 400 ng versus 250 ng bsDNA, reproducibility of the assay ranged from Spearmanr2=0.41to 0.90, indicating thatβ-values obtained with a lower DNA amount did not always correlate well with the higher amount. Average methylation for the six samples was higher using 250 ng (β-value = 0.45,SD=0.29) than with 400 ng (β-value = 0.36,SD=0.32). Reproducibility between duplicate HapMap samples (r2=0.76to 0.92) was also variable. Using 400 ng input bsDNA,THBS2andERGwere differentially methylated across all histologic types and between endometrioid and clear cell types at <0.1% false discovery rate. Methylation did not always correlate with gene expression (r2=-0.70to 0.15). We found that lower bsDNA overestimates methylation, and, using higher bsDNA amounts, we confirmed a previous report of higher methylation ofTHBS2in clear cell OC, which could provide new insight into biological pathways that distinguish OC histological types.

Author(s):  
Keiichi Fujiwara ◽  
Jessica N. McAlpine ◽  
Stephanie Lheureux ◽  
Noriomi Matsumura ◽  
Amit M. Oza

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.


2008 ◽  
Vol 109 (3) ◽  
pp. 370-376 ◽  
Author(s):  
John K. Chan ◽  
Deanna Teoh ◽  
Jessica M. Hu ◽  
Jacob Y. Shin ◽  
Kathryn Osann ◽  
...  

Author(s):  
Javier de la Torre Fernández de Vega ◽  
Jose Luis Sánchez-Iglesias ◽  
Assumpt Perez-Benavente ◽  
Antonio Gil-Moreno ◽  
Rasheda Begum Dina ◽  
...  

Epithelial ovarian cancer presents different histological subtypes, mainly serous, mucinous, endometriod, clear cell, mixed and undifferentiated cell. Molecular genetic studies have led to a new paradigm based on a dualistic model of ovarian carcinogenesis. There is a causal association between endometriosis and specific types of ovarian carcinomas, but the magnitude of the risk is low and endometriosis is not considered a premalignant lesion. Among the endometriosis-associated ovarian tumors adenocarcinoma is the most common (Endometrioid and clear cell) (70%), sarcoma is the second most common malignancy (12%) and rare cell types 6%. The gynecologist should pay special attention to identify patients with endometriosis who may be at an increased risk for ovarian cancer.


2009 ◽  
Vol 133 (11) ◽  
pp. 1775-1781 ◽  
Author(s):  
Kathleen R. Cho

Abstract Ovarian carcinomas are a heterogeneous group of neoplasms. Pathologists currently employ a morphology-based classification system to divide ovarian carcinomas into major subgroups based on degree (tumor grade) and type of differentiation (eg, serous, endometrioid, clear cell, or mucinous). Molecular studies have shown that specific genetic defects are likely to be present in certain histologic types of ovarian carcinomas and unlikely to be present in others. Within the serous and endometrioid carcinomas, the molecular defects in low-grade versus high-grade tumors also appear to be largely distinct. Recently, mouse models of ovarian carcinoma have been developed that recapitulate many of the morphologic features and biologic behavior of selected subtypes of ovarian cancer. It is expected that these mouse models will yield new insights into ovarian cancer pathogenesis and prove useful for preclinical testing of novel strategies for ovarian cancer treatment.


2020 ◽  
Author(s):  
L Feil ◽  
J Senz ◽  
M Ta ◽  
J Huvila ◽  
K Greif ◽  
...  

2007 ◽  
Vol 38 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Sadako Nishimura ◽  
Hiroshi Tsuda ◽  
Kiyoshi Ito ◽  
Toshiko Jobo ◽  
Nobuo Yaegashi ◽  
...  

1992 ◽  
Vol 12 (1) ◽  
pp. 220-228
Author(s):  
J A Mietz ◽  
J W Fewell ◽  
E L Kuff

Intracisternal A-particle (IAP) proviral elements are abundant and widely dispersed in the mouse genome. IAP-related transcripts have been detected in normal mouse tissues where expression is under genetic control. In this study, we sought to determine whether IAP expression in BALB/c thymus and lipopolysaccharide-stimulated B cells was due to selective or indiscriminate activation of IAP elements. cDNA libraries were prepared from each source. A total of 86 IAP cDNA clones were isolated from both libraries, and 37 of these were sequenced over a common 0.7- to 1.0-kb region of the IAP genome that included the 3' long terminal repeat (LTR). Three highly related families of elements were found to be expressed in the two cell types examined. All of the related elements had a distinctive U3 regulatory region. Thirteen individual IAP proviral elements were distinguished on the basis of sequence differences within the R region of the LTR. Hybridization of genomic DNA with element-specific oligonucleotide probes confirmed the presence of a restricted number of proviral copies in the lymphocyte-specific family of elements. Most of these copies were found to be methylated in the lymphocyte DNA, but at least seven were hypomethylated in their 5' LTRs. This study shows that activation of IAP elements in normal normal mouse lymphocytes is highly selective. Activation is probably a function of both sequence specificity and methylation status of the proviral LTR.


1963 ◽  
Vol s3-104 (66) ◽  
pp. 197-205
Author(s):  
D. C. ROGERS

Epithelial body III of Tiliqua occipitalis and Trachysaurus rugosus has been the subject of a histological and cytochemical investigation with the object of making a comparison with the mammalian parathyroid gland. The cytochemical reactions of the reptilian chief cell are similar to those of the mammalian ‘pale principal’ cell. On the basis of a series of cytological and cytochemical changes a secretory cycle commencing with the chief cell and culminating in the water-clear cell is postulated. Two further cell types distinguished as the dark cell and the ‘epithelial’ cell have been described in the reptilian epithelial body. The significance of these two cell types is discussed. There is some evidence suggesting that true sinusoids invest the cellular cords. There is no evidence, with the technique used, that the gland cells are innervated. It is suggested that the general histology is comparable to that of the mammalian parathyroid gland.


Sign in / Sign up

Export Citation Format

Share Document