Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma

Guy A. Weiss, Michael R. Rossi, Nikhil I. Khushalani, Ken Lo, John F. Gibbs, Anubha Bharthuar, John Kenneth Cowell, Renuka Iyer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy. Methods: Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted. Results: No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2% and 10.5% in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6% and 11.7% of pancreatic and biliary tract carcinomas, respectively. Conclusions: A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5%), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalJournal of Gastrointestinal Oncology
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2013

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Phosphatidylinositol 3-Kinase
erbB-1 Genes
Epidermal Growth Factor Receptor
Catalytic Domain
Adenocarcinoma
Mutation
Biliary Tract
Carcinoma
Single Nucleotide Polymorphism
Exons
Neoplasms
Pancreatectomy
Mutation Rate
Pancreatic Neoplasms
Non-Small Cell Lung Carcinoma
Paraffin
Introns
Formaldehyde
Cell Survival
Cross-Sectional Studies

Keywords

  • Biliary
  • Cancer
  • Epidermal growth factor receptor (EGFR)
  • Mutations
  • Pancreas
  • Phosphatidylinositol-3-kinase catalytic subunit (PIK3CA)

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma. / Weiss, Guy A.; Rossi, Michael R.; Khushalani, Nikhil I.; Lo, Ken; Gibbs, John F.; Bharthuar, Anubha; Cowell, John Kenneth; Iyer, Renuka.

In: Journal of Gastrointestinal Oncology, Vol. 4, No. 1, 01.01.2013, p. 20-29.

Research output: Contribution to journalArticle

Weiss, Guy A. ; Rossi, Michael R. ; Khushalani, Nikhil I. ; Lo, Ken ; Gibbs, John F. ; Bharthuar, Anubha ; Cowell, John Kenneth ; Iyer, Renuka. / Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma. In: Journal of Gastrointestinal Oncology. 2013 ; Vol. 4, No. 1. pp. 20-29.
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abstract = "Background: Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy. Methods: Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted. Results: No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2{\%} and 10.5{\%} in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6{\%} and 11.7{\%} of pancreatic and biliary tract carcinomas, respectively. Conclusions: A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5{\%}), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.",
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T1 - Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma

AU - Weiss, Guy A.

AU - Rossi, Michael R.

AU - Khushalani, Nikhil I.

AU - Lo, Ken

AU - Gibbs, John F.

AU - Bharthuar, Anubha

AU - Cowell, John Kenneth

AU - Iyer, Renuka

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy. Methods: Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted. Results: No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2% and 10.5% in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6% and 11.7% of pancreatic and biliary tract carcinomas, respectively. Conclusions: A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5%), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.

AB - Background: Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy. Methods: Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted. Results: No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2% and 10.5% in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6% and 11.7% of pancreatic and biliary tract carcinomas, respectively. Conclusions: A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5%), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.

KW - Biliary

KW - Cancer

KW - Epidermal growth factor receptor (EGFR)

KW - Mutations

KW - Pancreas

KW - Phosphatidylinositol-3-kinase catalytic subunit (PIK3CA)

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