Somatic mutation and gain of copy number of PIK3CA in human breast cancer

Guojun Wu, Mingzhao Xing, Elizabeth Mambo, Xin Huang, Junwei Liu, Zhongmin Guo, Aditi Chatterjee, David Goldenberg, Susanne M. Gollin, Saraswati Sukumar, Barry Trink, David Sidransky

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Abstract

Introduction: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. Methods: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. Results: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. Conclusion: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.

Original languageEnglish (US)
Article numberR609
JournalBreast Cancer Research
Volume7
Issue number5
DOIs
StatePublished - May 31 2005

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Breast Neoplasms
Gene Dosage
Mutation
Apoptosis
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Medical Genetics
Mutation Rate
Tumor Cell Line
Fluorescence In Situ Hybridization
Phosphatidylinositol 3-Kinases
Cell Adhesion
Colonic Neoplasms
Real-Time Polymerase Chain Reaction
Exons
Neoplasms
Phosphotransferases
Phosphorylation
Cell Proliferation
Lipids
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Wu, G., Xing, M., Mambo, E., Huang, X., Liu, J., Guo, Z., ... Sidransky, D. (2005). Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Research, 7(5), [R609]. https://doi.org/10.1186/bcr1262
Wu, Guojun ; Xing, Mingzhao ; Mambo, Elizabeth ; Huang, Xin ; Liu, Junwei ; Guo, Zhongmin ; Chatterjee, Aditi ; Goldenberg, David ; Gollin, Susanne M. ; Sukumar, Saraswati ; Trink, Barry ; Sidransky, David. / Somatic mutation and gain of copy number of PIK3CA in human breast cancer. In: Breast Cancer Research. 2005 ; Vol. 7, No. 5.
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abstract = "Introduction: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. Methods: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. Results: We identified a 20.6{\%} (19 of 92) and 33.3{\%} (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7{\%} (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. Conclusion: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.",
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Wu, G, Xing, M, Mambo, E, Huang, X, Liu, J, Guo, Z, Chatterjee, A, Goldenberg, D, Gollin, SM, Sukumar, S, Trink, B & Sidransky, D 2005, 'Somatic mutation and gain of copy number of PIK3CA in human breast cancer', Breast Cancer Research, vol. 7, no. 5, R609. https://doi.org/10.1186/bcr1262

Somatic mutation and gain of copy number of PIK3CA in human breast cancer. / Wu, Guojun; Xing, Mingzhao; Mambo, Elizabeth; Huang, Xin; Liu, Junwei; Guo, Zhongmin; Chatterjee, Aditi; Goldenberg, David; Gollin, Susanne M.; Sukumar, Saraswati; Trink, Barry; Sidransky, David.

In: Breast Cancer Research, Vol. 7, No. 5, R609, 31.05.2005.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Somatic mutation and gain of copy number of PIK3CA in human breast cancer

AU - Wu, Guojun

AU - Xing, Mingzhao

AU - Mambo, Elizabeth

AU - Huang, Xin

AU - Liu, Junwei

AU - Guo, Zhongmin

AU - Chatterjee, Aditi

AU - Goldenberg, David

AU - Gollin, Susanne M.

AU - Sukumar, Saraswati

AU - Trink, Barry

AU - Sidransky, David

PY - 2005/5/31

Y1 - 2005/5/31

N2 - Introduction: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. Methods: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. Results: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. Conclusion: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.

AB - Introduction: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. Methods: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. Results: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. Conclusion: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.

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DO - 10.1186/bcr1262

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