Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer

Ana M. Gonzalez-Angulo, Huiqin Chen, Meghan S. Karuturi, Mariana Chavez-Macgregor, Spyrus Tsavachidis, Funda Meric-Bernstam, Kim Anh Do, Gabriel N. Hortobagyi, Patricia A. Thompson, Gordon Mills, Melissa L. Bondy, George R. Blumenschein

Research output: Contribution to journalArticle

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Abstract

Background: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer. Methods: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS. Results: Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P =.019 and P <.001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P =.06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P =.15). A high copy number for either gene was not found to be an independent predictor of RFS. Conclusions: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalCancer
Volume119
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Epithelial-Mesenchymal Transition
1-Phosphatidylinositol 4-Kinase
Catalytic Domain
Breast Neoplasms
Recurrence
Genes
Survival
Neoplasms
Molecular Probes
Gene Dosage
Proportional Hazards Models
Paraffin
Formaldehyde
Single Nucleotide Polymorphism
Survival Rate
Hormones
DNA

Keywords

  • breast cancer
  • catalytic subunit of phosphoinositide-3-kinase (PIK3CA)
  • gene copy number
  • MET
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer. / Gonzalez-Angulo, Ana M.; Chen, Huiqin; Karuturi, Meghan S.; Chavez-Macgregor, Mariana; Tsavachidis, Spyrus; Meric-Bernstam, Funda; Do, Kim Anh; Hortobagyi, Gabriel N.; Thompson, Patricia A.; Mills, Gordon; Bondy, Melissa L.; Blumenschein, George R.

In: Cancer, Vol. 119, No. 1, 01.01.2013, p. 7-15.

Research output: Contribution to journalArticle

Gonzalez-Angulo, AM, Chen, H, Karuturi, MS, Chavez-Macgregor, M, Tsavachidis, S, Meric-Bernstam, F, Do, KA, Hortobagyi, GN, Thompson, PA, Mills, G, Bondy, ML & Blumenschein, GR 2013, 'Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer', Cancer, vol. 119, no. 1, pp. 7-15. https://doi.org/10.1002/cncr.27608
Gonzalez-Angulo, Ana M. ; Chen, Huiqin ; Karuturi, Meghan S. ; Chavez-Macgregor, Mariana ; Tsavachidis, Spyrus ; Meric-Bernstam, Funda ; Do, Kim Anh ; Hortobagyi, Gabriel N. ; Thompson, Patricia A. ; Mills, Gordon ; Bondy, Melissa L. ; Blumenschein, George R. / Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer. In: Cancer. 2013 ; Vol. 119, No. 1. pp. 7-15.
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title = "Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer",
abstract = "Background: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer. Methods: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS. Results: Of the 971 tumors studied, 82 (8.44{\%}) and 134 (13.8{\%}) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6{\%} of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P =.019 and P <.001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5{\%} and 83.1{\%} for MET high copy number and MET normal/low copy number, respectively (P =.06) and 73.1{\%}, and 82.3{\%} for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P =.15). A high copy number for either gene was not found to be an independent predictor of RFS. Conclusions: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.",
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T1 - Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer

AU - Gonzalez-Angulo, Ana M.

AU - Chen, Huiqin

AU - Karuturi, Meghan S.

AU - Chavez-Macgregor, Mariana

AU - Tsavachidis, Spyrus

AU - Meric-Bernstam, Funda

AU - Do, Kim Anh

AU - Hortobagyi, Gabriel N.

AU - Thompson, Patricia A.

AU - Mills, Gordon

AU - Bondy, Melissa L.

AU - Blumenschein, George R.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer. Methods: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS. Results: Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P =.019 and P <.001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P =.06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P =.15). A high copy number for either gene was not found to be an independent predictor of RFS. Conclusions: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.

AB - Background: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer. Methods: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS. Results: Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P =.019 and P <.001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P =.06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P =.15). A high copy number for either gene was not found to be an independent predictor of RFS. Conclusions: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.

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KW - catalytic subunit of phosphoinositide-3-kinase (PIK3CA)

KW - gene copy number

KW - MET

KW - prognosis

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