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Title: Aberrations of DPPA3 (STELLA), EDR1 (PHC1), GDF3, and NANOG, putative stem cell-associated genes on chromosome 12, in breast carcinoma
Author: Ruangpratheep, Chetana
ISNI:       0000 0004 2723 0957
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2012
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Introduction: Chromosome 12p13 has been reported to show gain/amplification in some breast cancers. This region contains putative stem cell-associated genes: DPPA3, EDR1, GDF3, and NANOG, but these genes have not been investigated in breast previously. Hence, the aim of this thesis was to study their role in breast carcinomas. Materials and methods: The mRNA expression was evaluated in normal and malignant breast tissues using TaqMan® gene expression assays. Western blotting and immunohistochemistry were used for determination of protein expression. Copy number variations (CNVs) were assessed by TaqMan® copy number assays (CNAs) and Affymetrix® genome-wide human single nucleotide polymorphism (SNP) array 6.0. Results: Expression of DPPA3, EDR1, and NANOG was undetectable in normal breast tissue, but there was variable expression in breast carcinomas (BC) where expression of these genes tended to be higher in surrounding normal breast tissue. GDF3 was not expressed in BC. At the 95% confidence interval, higher expression of DPPA3 in BC was related to axillary lymph node metastasis; lower expression of DPPA3, EDR1, and NANOG correlated with high grade; and lower expression of NANOG was found in tumours of size > 2.0 cm. Both TaqMan® CNAs targeting each gene individually and SNP 6.0 genome wide array revealed complicated patterns of CNVs for these genes. The majority of BC had gain of DPPA3 but loss (deletion) of EDR1 and NANOG. However, there was no significant correlation between CNVs and either mRNA expression or protein expression. Conclusion: Variable aberrations in copy number and expression of DPPA3, EDR1, and NANOG genes in the chromosome 12p13 region are associated with aggressive characteristics of breast carcinomas.
Supervisor: Shaw, Jacqueline. ; Walker, Rosemary. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available