Integrative genomics approach identifies molecular features associated with early-stage ovarian carcinoma histotypes

Engqvist, Hanna; Parris, Toshima Z.; Biermann, Jana; Rönnerman, Elisabeth Werner; Larsson, Peter; Sundfeldt, Karin; Kovács, Anikó; Karlsson, Per; Helou, Khalil

doi:10.1038/s41598-020-64794-8

Cited by 16 publications

(17 citation statements)

References 37 publications

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“…MOC showed the highest average number of copy number alterations. RNA expression was able to classify the different histotypes, but the differences were more evident when using the DNA methylation heatmap [49].…”

Section: Availability Of Cell Culture Models For Studying Common and Rare Ovarian Cancersmentioning

confidence: 97%

(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

Sabol

Calleja‐Agius

Fiore

et al. 2021

Cancers

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Rare ovarian cancers (ROCs) are OCs with an annual incidence of fewer than 6 cases per 100,000 women. They affect women of all ages, but due to their low incidence and the potential clinical inexperience in management, there can be a delay in diagnosis, leading to a poor prognosis. The underlying causes for these tumors are varied, but generally, the tumors arise due to alterations in gene/protein expression in cellular processes that regulate normal proliferation and its checkpoints. Dysregulation of the cellular processes that lead to cancer includes gene mutations, epimutations, non-coding RNA (ncRNA) regulation, posttranscriptional and posttranslational modifications. Long non-coding RNA (lncRNA) are defined as transcribed RNA molecules, more than 200 nucleotides in length which are not translated into proteins. They regulate gene expression through several mechanisms and therefore add another level of complexity to the regulatory mechanisms affecting tumor development. Since few studies have been performed on ROCs, in this review we summarize the mechanisms of action of lncRNA in OC, with an emphasis on ROCs.

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Section: Availability Of Cell Culture Models For Studying Common and Rare Ovarian Cancersmentioning

confidence: 97%

(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

Sabol

Calleja‐Agius

Fiore

et al. 2021

Cancers

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“…Finally, a number of recent studies have used integrative analyses to identify novel oncogenes and tumor suppressors that promote HGSOC and biomarkers to predict therapeutic response and risk. These studies relied on integrative analyses of DNA copy number, methylation, and gene expression data to identify potential oncogenes and tumor suppressor proteins in HGSOC and clear cell carcinoma [ 125 , 126 , 127 ]. Similarly, studies from Karagoz et al assessed orthogonal genomic and proteomic data from human HGSOC tumors from the TCGA and CPTAC studies in the context of a prognosis gene expression signature.…”

Section: Molecular Classification and Characterization Of Ovarian mentioning

confidence: 99%

Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

Khella

Mehta

et al. 2021

JPM

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The underlying molecular heterogeneity of cancer is responsible for the dynamic clinical landscape of this disease. The combination of genomic and proteomic alterations, including both inherited and acquired mutations, promotes tumor diversity and accounts for variable disease progression, therapeutic response, and clinical outcome. Recent advances in high-throughput proteogenomic profiling of tumor samples have resulted in the identification of novel oncogenic drivers, tumor suppressors, and signaling networks; biomarkers for the prediction of drug sensitivity and disease progression; and have contributed to the development of novel and more effective treatment strategies. In this review, we will focus on the impact of historical and recent advances in single platform and integrative proteogenomic studies in breast and ovarian cancer, which constitute two of the most lethal forms of cancer for women, and discuss the molecular similarities of these diseases, the impact of these findings on our understanding of tumor biology as well as the clinical applicability of these discoveries.

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“…Conversely, endometrioid ovarian cancer (ENOC) is characterized by frequent promoter hypermethylation (CpG island methylation phenotype, CIMP) that is also common in uterine endometrioid tumors and parsimonious with the hypothesized endometriosis origin of ENOC [ 24 ]. Clear cell ovarian cancer (CCOC) also distinguishes itself by displaying the highest frequency (>70%) of hypermethylation [ 25 ]. It is important to note that differences in tumor DNAm may be associated with response to chemotherapy and prognosis.…”

Section: Dna Methylation In Epigenetic Control and Heritabilitymentioning

confidence: 99%

DNA Methylation in Ovarian Cancer Susceptibility

Reid

Fridley

2020

Cancers

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Epigenetic alterations are somatically acquired over the lifetime and during neoplastic transformation but may also be inherited as widespread ‘constitutional’ alterations in normal tissues that can cause cancer predisposition. Epithelial ovarian cancer (EOC) has an established genetic susceptibility and mounting epidemiological evidence demonstrates that DNA methylation (DNAm) intermediates as well as independently contributes to risk. Targeted studies of known EOC susceptibility genes (CSGs) indicate rare, constitutional BRCA1 promoter methylation increases familial and sporadic EOC risk. Blood-based epigenome-wide association studies (EWAS) for EOC have detected a total of 2846 differentially methylated probes (DMPs) with 71 genes replicated across studies despite significant heterogeneity. While EWAS detect both symptomatic and etiologic DMPs, adjustments and analytic techniques may enrich risk associations, as evidenced by the detection of dysregulated methylation of BNC2—a known CSG identified by genome-wide associations studies (GWAS). Integrative genetic–epigenetic approaches have mapped methylation quantitative trait loci (meQTL) to EOC risk, revealing DNAm variations that are associated with nine GWAS loci and, further, one novel risk locus. Increasing efforts to mapping epigenome variation across populations and cell types will be key to decoding both the genomic and epigenomic causal pathways to EOC.

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Integrative genomics approach identifies molecular features associated with early-stage ovarian carcinoma histotypes

Cited by 16 publications

References 37 publications

(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

DNA Methylation in Ovarian Cancer Susceptibility

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