scholarly journals Telomeres and Genomic Instability from Precancerous Lesions to Advanced Cancer – Understanding Through Ovarian Cancer

10.5772/62259 ◽  
2016 ◽  
Author(s):  
Gautier Chene ◽  
Gery Lamblin ◽  
Karine Le Bail-Carval ◽  
Philippe Chabert ◽  
Georges Mellier ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genomic Instability ◽  
Advanced Cancer ◽  
Precancerous Lesions

scholarly journals Precancerous Lesions of Ovarian Cancer—A US Perspective

2017 ◽  
Vol 110 (7) ◽  
pp. 692-693 ◽  
Author(s):  
Kala Visvanathan ◽  
Tian-Li Wang ◽  
Ie-Ming Shih
Keyword(s):  
Ovarian Cancer ◽  
Precancerous Lesions

scholarly journals Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla—Site of Origin of Serous Carcinoma of the Ovary

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1090
Author(s):  
Ramlogan Sowamber ◽  
Omar Nelson ◽  
Leah Dodds ◽  
Victoria DeCastro ◽  
Iru Paudel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Precancerous Lesions ◽  
Expression Profiles ◽  
Premenopausal Women ◽  
Serous Carcinoma ◽  
Ovarian Cancer Risk ◽  
Transcriptional Responses ◽  
Human Fallopian Tube ◽  
Transcriptional Changes

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.

scholarly journals Global DNA Hypomethylation in Epithelial Ovarian Cancer: Passive Demethylation and Association with Genomic Instability

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 764 ◽  
Author(s):  
Wa Zhang ◽  
David Klinkebiel ◽  
Carter J. Barger ◽  
Sanjit Pandey ◽  
Chittibabu Guda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Genomic Instability ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Gene Expression Signature ◽  
Dna Methyltransferases ◽  
Dna Demethylation ◽  
Dna Hypomethylation ◽  
Proliferation Markers

A hallmark of human cancer is global DNA hypomethylation (GDHO), but the mechanisms accounting for this defect and its pathological consequences have not been investigated in human epithelial ovarian cancer (EOC). In EOC, GDHO was associated with advanced disease and reduced overall and disease-free survival. GDHO (+) EOC tumors displayed a proliferative gene expression signature, including FOXM1 and CCNE1 overexpression. Furthermore, DNA hypomethylation in these tumors was enriched within genomic blocks (hypomethylated blocks) that overlapped late-replicating regions, lamina-associated domains, PRC2 binding sites, and the H3K27me3 histone mark. Increased proliferation coupled with hypomethylated blocks at late-replicating regions suggests a passive hypomethylation mechanism. This hypothesis was further supported by our observation that cytosine DNA methyltransferases (DNMTs) and UHRF1 showed significantly reduced expression in GDHO (+) EOC after normalization to canonical proliferation markers, including MKI67. Finally, GDHO (+) EOC tumors had elevated chromosomal instability (CIN), and copy number alterations (CNA) were enriched at the DNA hypomethylated blocks. Together, these findings implicate a passive DNA demethylation mechanism in ovarian cancer that is associated with genomic instability and poor prognosis.

Integration of specialty palliative care in a phase I ovarian cancer population.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 75-75
Author(s):  
Marisa R Moroney ◽  
Breana Hill ◽  
Jeanelle Sheeder ◽  
Jennifer Robinson Diamond ◽  
Melony Avella-Howell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Palliative Care ◽  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Disease Stage ◽  
Phase I Clinical Trials ◽  
Care Services ◽  
Palliative Care Services

75 Background: ASCO guidelines recommend patients with advanced cancer receive early integrated specialty palliative care based on evidence of multiple clinical benefits. To our knowledge, there is no literature evaluating utilization of specialty palliative care in Phase I clinical trial patients, but there is limited data demonstrating underutilization of palliative care services in patients with life-threatening diseases including advanced cancer. Methods: A retrospective review of ovarian cancer patients enrolled in Phase I clinical trials at one institution from 2008 to 2018. Charts were reviewed for patient and disease characteristics including age, disease stage, number of chemotherapy regimens and date of death. Charts were also reviewed to determine if and when patients received specialty palliative care services. Results: A total of 121 patients with ovarian cancer were enrolled in Phase I clinical trials. Median age at time of Phase I enrollment was 59 years (range 33-88). 87% of patients had advanced stage disease: 60% Stage III and 27% Stage IV. Median number of chemotherapy regimens received prior to Phase I enrollment was 5 (range 1-13). Median survival was 311 days (95%CI 225.9-396.1). Of the 121 patients, 4 (3.3%) received specialty palliative care prior to Phase I enrollment, 7 (5.8%) within 30 days after enrollment, and 53 (43.8%) more than 30 days after enrollment. 57 patients (47.1%) never received specialty palliative care. Conclusions: Ovarian cancer patients enrolled in Phase I clinical trials have advanced cancer – defined by ASCO as disease that is late-stage and life limiting with a prognosis less than 24 months – and should therefore receive early integrated specialty palliative care. This study demonstrates that a significant portion of Phase I ovarian cancer patients are either receiving no or late integration of specialty palliative care. Further work needs to focus on increasing early integration of specialty palliative care in this population.

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