ORCID Profile
0000-0002-1395-9734
Current Organisation
University of Limerick
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Publisher: Oxford University Press (OUP)
Date: 18-01-2012
DOI: 10.1093/JNCI/DJR545
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
Publisher: American Association for Cancer Research (AACR)
Date: 14-10-2012
DOI: 10.1158/1078-0432.CCR-12-0857
Abstract: Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR causes uniparental deletions and loss of heterozygosity (LOH). Our purpose is to profile LOH in HGSC and correlate our findings to clinical outcome, and compare HGSC and high-grade breast cancers. Experimental Design: We examined LOH and copy number changes using single nucleotide polymorphism array data from three HGSC cohorts and compared results to a cohort of high-grade breast cancers. The LOH profiles in HGSC were matched to chemotherapy resistance and progression-free survival (PFS). Results: LOH-based clustering ided HGSC into two clusters. The major group displayed extensive LOH and was further ided into two subgroups. The second group contained remarkably less LOH. BRCA1 promoter methylation was associated with the major group. LOH clusters were reproducible when validated in two independent HGSC datasets. LOH burden in the major cluster of HGSC was similar to triple-negative, and distinct from other high-grade breast cancers. Our analysis revealed an LOH cluster with lower treatment resistance and a significant correlation between LOH burden and PFS. Conclusions: Separating HGSC by LOH-based clustering produces remarkably stable subgroups in three different cohorts. Patients in the various LOH clusters differed with respect to chemotherapy resistance, and the extent of LOH correlated with PFS. LOH burden may indicate vulnerability to treatment targeting DNA repair, such as PARP1 inhibitors. Clin Cancer Res 18(20) 5806–15. ©2012 AACR.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Public Library of Science (PLoS)
Date: 11-03-2013
Publisher: Oxford University Press (OUP)
Date: 04-2004
Publisher: Springer Science and Business Media LLC
Date: 28-01-2009
DOI: 10.1038/NG.295
Abstract: Given the complexity of microarray-based gene expression studies, guidelines encourage transparent design and public data availability. Several journals require public data deposition and several public databases exist. However, not all data are publicly available, and even when available, it is unknown whether the published results are reproducible by independent scientists. Here we evaluated the replication of data analyses in 18 articles on microarray-based gene expression profiling published in Nature Genetics in 2005-2006. One table or figure from each article was independently evaluated by two teams of analysts. We reproduced two analyses in principle and six partially or with some discrepancies ten could not be reproduced. The main reason for failure to reproduce was data unavailability, and discrepancies were mostly due to incomplete data annotation or specification of data processing and analysis. Repeatability of published microarray studies is apparently limited. More strict publication rules enforcing public data availability and explicit description of data processing and analysis should be considered.
Publisher: American Association for Cancer Research (AACR)
Date: 2016
DOI: 10.1158/2159-8290.CD-15-0341
Abstract: An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified methyl cytosine-guanine dinucleotide (CpG) binding protein 2 (MECP2) as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly lified across 18% of cancers, and many cancer cell lines have lified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy-number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRASG12C-addicted cell line after KRAS downregulation, and activated KRAS rescues the growth of an MECP2-addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly lified oncogene with an unusual epigenetic mode of action. Significance: MECP2 is a commonly lified oncogene in human malignancies with a unique epigenetic mechanism of action. Cancer Discov 6(1) 45–58. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 1
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 08-2019
Publisher: American Association for Cancer Research (AACR)
Date: 16-07-2021
DOI: 10.1158/1055-9965.EPI-21-0266
Abstract: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2020
DOI: 10.1038/S41467-020-18849-Z
Abstract: Comorbid conditions appear to be common among in iduals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 in iduals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of in iduals being hospitalised with COVID-19.
Publisher: Oxford University Press (OUP)
Date: 24-11-2011
DOI: 10.1093/NAR/GKR1051
Location: No location found
Location: No location found
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Aedin Culhane.