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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer
Jennifer A Byrne1, Rosemary L Balleine, Marlena Schoenberg Fejzo
1Molecular Oncology Laboratory, Oncology Research Unit, The University of Sydney Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, New South Wales, Australia. jennifeb@chw.edu.au
Abstract:
Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 amplification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas. In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses. This revealed that TPD52 dosage and TPD52 expression were significantly positively correlated. TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number.
Insights
Tumor Protein D52 (TPD52) is overexpressed in most ovarian cancers, unlike normal tissues. This overexpression correlates with increased TPD52 gene copy number, suggesting TPD52 as a novel ovarian cancer marker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Recurrent chromosome 8q gain in ovarian cancer suggests multiple target genes.
- Tumor Protein D52 (TPD52) is an 8q21 amplification target in other cancers.
Purpose of the Study:
- To investigate TPD52 expression and its correlation with gene copy number in ovarian cancer.
- To evaluate TPD52 as a potential molecular marker for ovarian carcinoma.
Main Methods:
- Immunohistochemistry to assess TPD52 protein expression in normal ovarian epithelium, benign tumors, and ovarian carcinomas.
- Interphase Fluorescence In Situ Hybridization (FISH) to determine TPD52 copy number in a subset of tumors.
Main Results:
- TPD52 was negative in normal ovarian epithelium and benign tumors.
- TPD52 was overexpressed in 77% of ovarian carcinomas across various subtypes.
- TPD52 expression positively correlated with TPD52 gene copy number.
Conclusions:
- TPD52 is a novel molecular marker for ovarian cancer.
- TPD52 upregulation in ovarian cancer frequently reflects increased gene copy number.
- TPD52 is broadly expressed across different ovarian carcinoma histologic subtypes.
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