Person:
Flavin, Richard John

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Flavin

First Name

Richard John

Name

Flavin, Richard John
Author's Publications: search.filters.isAuthorOfPublication.f6c27df5-de16-4f11-82bb-4fc6e0412a6f

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in Human Prostate Tumorigenesis
    (Public Library of Science, 2010) Chanock, Stephen J.; Schafer, Eric J.; Tabernero, Josep; Baselga, José; Oh, William K.; Pomerantz, Mark; Shrestha, Yashaswi; Flavin, Richard John; Regan, Meredith; Penney, Kathryn; Mucci, Lorelei; Stampfer, Meir; Hunter, David; Chan, Jennifer; Richardson, Andrea; Loda, Massimo; Kantoff, Philip; Hahn, William; Freedman, Matthew
    Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states.
  • Thumbnail Image
    Publication
    Potential Role of miR-9 and miR-223 in Recurrent Ovarian Cancer
    (BioMed Central, 2008) Laios, Alexandros; O'Toole, Sharon; Martin, Cara; Kelly, Lynn; Ring, Martina; Finn, Stephen P; Barrett, Ciara; Gleeson, Noreen; D'Arcy, Tom; McGuinness, Eamonn; Sheils, Orla; O' Leary, John; Flavin, Richard John; Loda, Massimo; Sheppard, Brian
    Background: MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease. Results: Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry. Conclusion: We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.