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Open Access 01-12-2005 | Research article

Aberrations of TACC1 and TACC3 are associated with ovarian cancer

Authors: Brenda Lauffart, Mary M Vaughan, Roger Eddy, David Chervinsky, Richard A DiCioccio, Jennifer D Black, Ivan H Still

Published in: BMC Women's Health | Issue 1/2005

Abstract

Background

Dysregulation of the human Transforming Acidic Coiled Coil (TACC) genes is thought to be important in the development and progression of multiple myeloma, breast and gastric cancer. Recent, large-scale genomic analysis and Serial Analysis of Gene Expression data suggest that TACC1 and TACC3 may also be involved in the etiology of ovarian tumors from both familial and sporadic cases. Therefore, the aim of this study was to determine the occurrence of alterations of these TACCs in ovarian cancer.

Methods

Detection and scoring of TACC1 and TACC3 expression was performed by immunohistochemical analysis of the T-BO-1 tissue/tumor microarray slide from the Cooperative Human Tissue Network, Tissue Array Research Program (TARP) of the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Tumors were categorized as either positive (greater than 10% of cells staining) or negative. Statistical analysis was performed using Fisher's exact test and p < 0.05 (single comparisons), and p < 0.02 (multiple comparisons) were considered to be significant. Transgenomics WAVE high performance liquid chromatography (dHPLC) was used to pre-screen the TACC3 gene in constitutional DNA from ovarian cancer patients and their unaffected relatives from 76 families from the Gilda Radner Familial Ovarian Cancer Registry. All variant patterns were then sequenced.

Results

This study demonstrated absence of at least one or both TACC proteins in 78.5% (51/65) of ovarian tumors tested, with TACC3 loss observed in 67.7% of tumors. The distribution pattern of expression of the two TACC proteins was different, with TACC3 loss being more common in serous papillary carcinoma compared with clear cell carcinomas, while TACC1 staining was less frequent in endometroid than in serous papillary tumor cores. In addition, we identified two constitutional mutations in the TACC3 gene in patients with ovarian cancer from the Gilda Radner Familial Ovarian Cancer Registry. These patients had previously tested negative for mutations in known ovarian cancer predisposing genes.

Conclusion

When combined, our data suggest that aberrations of TACC genes, and TACC3 in particular, underlie a significant proportion of ovarian cancers. Thus, TACC3 could be a hitherto unknown endogenous factor that contributes to ovarian tumorigenesis.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/5/8/prepub

Title: Aberrations of TACC1 and TACC3 are associated with ovarian cancer
Authors: Brenda Lauffart
Mary M Vaughan
Roger Eddy
David Chervinsky
Richard A DiCioccio
Jennifer D Black
Ivan H Still
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: BMC Women's Health / Issue 1/2005
Electronic ISSN: 1472-6874
DOI: https://doi.org/10.1186/1472-6874-5-8

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Aberrations of TACC1 and TACC3 are associated with ovarian cancer

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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