Aberrations of TACC1 and TACC3 are associated with ovarian cancer

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

Research output: Contribution to journalArticle

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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. Conclusions: 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.

Original languageEnglish (US)
Article number8
JournalBMC Women's Health
Volume5
DOIs
StatePublished - May 26 2005

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Ovarian Neoplasms
Neoplasms
Genes
Registries
Negative Staining
Mutation
National Cancer Institute (U.S.)
Papillary Carcinoma
Neoplasm Genes
National Institutes of Health (U.S.)
Multiple Myeloma
Stomach Neoplasms
Carcinogenesis
Proteins
Research Design
High Pressure Liquid Chromatography
Staining and Labeling
Breast Neoplasms
Carcinoma
Gene Expression

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Lauffart, B., Vaughan, M. M., Eddy, R., Chervinsky, D., DiCioccio, R. A., Black, J. D., & Still, I. H. (2005). Aberrations of TACC1 and TACC3 are associated with ovarian cancer. BMC Women's Health, 5, [8]. https://doi.org/10.1186/1472-6874-5-8

Aberrations of TACC1 and TACC3 are associated with ovarian cancer. / Lauffart, Brenda; Vaughan, Mary M.; Eddy, Roger; Chervinsky, David; DiCioccio, Richard A.; Black, Jennifer D; Still, Ivan H.

In: BMC Women's Health, Vol. 5, 8, 26.05.2005.

Research output: Contribution to journalArticle

Lauffart, B, Vaughan, MM, Eddy, R, Chervinsky, D, DiCioccio, RA, Black, JD & Still, IH 2005, 'Aberrations of TACC1 and TACC3 are associated with ovarian cancer', BMC Women's Health, vol. 5, 8. https://doi.org/10.1186/1472-6874-5-8
Lauffart B, Vaughan MM, Eddy R, Chervinsky D, DiCioccio RA, Black JD et al. Aberrations of TACC1 and TACC3 are associated with ovarian cancer. BMC Women's Health. 2005 May 26;5. 8. https://doi.org/10.1186/1472-6874-5-8
Lauffart, Brenda ; Vaughan, Mary M. ; Eddy, Roger ; Chervinsky, David ; DiCioccio, Richard A. ; Black, Jennifer D ; Still, Ivan H. / Aberrations of TACC1 and TACC3 are associated with ovarian cancer. In: BMC Women's Health. 2005 ; Vol. 5.
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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. Conclusions: 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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AU - Lauffart, Brenda

AU - Vaughan, Mary M.

AU - Eddy, Roger

AU - Chervinsky, David

AU - DiCioccio, Richard A.

AU - Black, Jennifer D

AU - Still, Ivan H.

PY - 2005/5/26

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N2 - 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. Conclusions: 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.

AB - 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. Conclusions: 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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