Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer

Emmanuel E. Zervos, Stephan M. Tanner, Dana A. Osborne, Mark Bloomston, Alexander S. Rosemurgy, E. Christopher Ellison, W. Scott Melvin, Albert de la Chapelle

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. Patients and methods: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. Results: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. Conclusions: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

Original languageEnglish (US)
Pages (from-to)317-322
Number of pages6
JournalJournal of Surgical Research
Volume135
Issue number2
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Gene Expression
Genes
Genetic Predisposition to Disease
Pancreas
Neoplasms
Carcinogenesis
Complementary DNA
Keratin-19
Cell Line
Polymerase Chain Reaction
Calcium-Binding Proteins
Neuroendocrine Tumors
Chronic Pancreatitis
Sequence Analysis
Adenocarcinoma
Fatty Acids
Biopsy
Messenger RNA

Keywords

  • genetics
  • pancreatic cancer
  • representational difference analysis

ASJC Scopus subject areas

  • Surgery

Cite this

Zervos, E. E., Tanner, S. M., Osborne, D. A., Bloomston, M., Rosemurgy, A. S., Ellison, E. C., ... de la Chapelle, A. (2006). Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer. Journal of Surgical Research, 135(2), 317-322. https://doi.org/10.1016/j.jss.2006.03.022

Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer. / Zervos, Emmanuel E.; Tanner, Stephan M.; Osborne, Dana A.; Bloomston, Mark; Rosemurgy, Alexander S.; Ellison, E. Christopher; Melvin, W. Scott; de la Chapelle, Albert.

In: Journal of Surgical Research, Vol. 135, No. 2, 10.2006, p. 317-322.

Research output: Contribution to journalArticle

Zervos, EE, Tanner, SM, Osborne, DA, Bloomston, M, Rosemurgy, AS, Ellison, EC, Melvin, WS & de la Chapelle, A 2006, 'Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer', Journal of Surgical Research, vol. 135, no. 2, pp. 317-322. https://doi.org/10.1016/j.jss.2006.03.022
Zervos EE, Tanner SM, Osborne DA, Bloomston M, Rosemurgy AS, Ellison EC et al. Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer. Journal of Surgical Research. 2006 Oct;135(2):317-322. https://doi.org/10.1016/j.jss.2006.03.022
Zervos, Emmanuel E. ; Tanner, Stephan M. ; Osborne, Dana A. ; Bloomston, Mark ; Rosemurgy, Alexander S. ; Ellison, E. Christopher ; Melvin, W. Scott ; de la Chapelle, Albert. / Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer. In: Journal of Surgical Research. 2006 ; Vol. 135, No. 2. pp. 317-322.
@article{cd8beda3e59742639cdb067bc993f9b8,
title = "Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer",
abstract = "Background: Nearly 10{\%} of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or {"}familial{"} PCA. Patients and methods: We defined {"}familial{"} PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. Results: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. Conclusions: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.",
keywords = "genetics, pancreatic cancer, representational difference analysis",
author = "Zervos, {Emmanuel E.} and Tanner, {Stephan M.} and Osborne, {Dana A.} and Mark Bloomston and Rosemurgy, {Alexander S.} and Ellison, {E. Christopher} and Melvin, {W. Scott} and {de la Chapelle}, Albert",
year = "2006",
month = "10",
doi = "10.1016/j.jss.2006.03.022",
language = "English (US)",
volume = "135",
pages = "317--322",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Differential Gene Expression in Patients Genetically Predisposed to Pancreatic Cancer

AU - Zervos, Emmanuel E.

AU - Tanner, Stephan M.

AU - Osborne, Dana A.

AU - Bloomston, Mark

AU - Rosemurgy, Alexander S.

AU - Ellison, E. Christopher

AU - Melvin, W. Scott

AU - de la Chapelle, Albert

PY - 2006/10

Y1 - 2006/10

N2 - Background: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. Patients and methods: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. Results: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. Conclusions: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

AB - Background: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. Patients and methods: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. Results: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. Conclusions: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

KW - genetics

KW - pancreatic cancer

KW - representational difference analysis

UR - http://www.scopus.com/inward/record.url?scp=33748764388&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748764388&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2006.03.022

DO - 10.1016/j.jss.2006.03.022

M3 - Article

C2 - 16815451

AN - SCOPUS:33748764388

VL - 135

SP - 317

EP - 322

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -