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Advances in Brief

Discovery of New Markers of Cancer through Serial Analysis of Gene Expression

Prostate Stem Cell Antigen Is Overexpressed in Pancreatic Adenocarcinoma

Pedram Argani, Christophe Rosty, Robert E. Reiter, Robb E. Wilentz, Selva R. Murugesan, Steven D. Leach, Byungwoo Ryu, Halcyon G. Skinner, Michael Goggins, Elizabeth M. Jaffee, Charles J. Yeo, John L. Cameron, Scott E. Kern and Ralph H. Hruban
Pedram Argani
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Christophe Rosty
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Robert E. Reiter
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Robb E. Wilentz
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Selva R. Murugesan
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Steven D. Leach
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Byungwoo Ryu
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Halcyon G. Skinner
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Michael Goggins
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Elizabeth M. Jaffee
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Charles J. Yeo
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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John L. Cameron
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Scott E. Kern
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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Ralph H. Hruban
Departments of Pathology [P. A., C. R., R. E. W., S. R. M., H. G. S., M. G., S. E. K., R. H. H.], Surgery [S. D. L., C. J. Y., J. L. C.], Oncology [S. D. L., B. R., M. G., E. M. J., C. J. Y., S. E. K., R. H. H.], and Medicine [M. G.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, Maryland 21287 [H. G. S.]; and Department of Urology, University of California, Los Angeles, California 90095 [R. E. R.]
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DOI:  Published June 2001
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Abstract

Serial analysis of gene expression (SAGE) can be used to quantify gene expression in human tissues. Comparison of gene expression levels in neoplastic tissues with those seen in nonneoplastic tissues can, in turn, identify novel tumor markers. Such markers are urgently needed for highly lethal cancers like pancreatic adenocarcinoma, which typically presents at an incurable, advanced stage. The results of SAGE analyses of a large number of neoplastic and nonneoplastic tissues are now available online, facilitating the rapid identification of novel tumor markers. We searched an online SAGE database to identify genes preferentially expressed in pancreatic cancers as compared with normal tissues. SAGE libraries derived from pancreatic adenocarcinomas were compared with SAGE libraries derived from nonneoplastic tissues. Three promising tags were identified. Two of these tags corresponded to genes (lipocalin and trefoil factor 2) previously shown to be overexpressed in pancreatic carcinoma, whereas the third tag corresponded to prostate stem cell antigen (PSCA), a recently discovered gene thought to be largely restricted to prostatic basal cells and prostatic adenocarcinomas. PSCA was expressed in four of the six pancreatic cancer SAGE libraries, but not in the libraries derived from normal pancreatic ductal cells. We confirmed the overexpression of the PSCA mRNA transcript in 14 of 19 pancreatic cancer cell lines by reverse transcription-PCR, and using immunohistochemistry, we demonstrated PSCA protein overexpression in 36 of 60 (60%) primary pancreatic adenocarcinomas. In 59 of 60 cases, the adjacent nonneoplastic pancreas did not label for PSCA. PSCA is a novel tumor marker for pancreatic carcinoma that has potential diagnostic and therapeutic implications. These results establish the validity of analyses of SAGE databases to identify novel tumor markers.

  • Received February 22, 2001.
  • Accepted April 12, 2001.
  • ©2001 American Association for Cancer Research.
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Cancer Research: 61 (11)
June 2001
Volume 61, Issue 11
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Discovery of New Markers of Cancer through Serial Analysis of Gene Expression
Pedram Argani, Christophe Rosty, Robert E. Reiter, Robb E. Wilentz, Selva R. Murugesan, Steven D. Leach, Byungwoo Ryu, Halcyon G. Skinner, Michael Goggins, Elizabeth M. Jaffee, Charles J. Yeo, John L. Cameron, Scott E. Kern and Ralph H. Hruban
Cancer Res June 1 2001 (61) (11) 4320-4324;

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Discovery of New Markers of Cancer through Serial Analysis of Gene Expression
Pedram Argani, Christophe Rosty, Robert E. Reiter, Robb E. Wilentz, Selva R. Murugesan, Steven D. Leach, Byungwoo Ryu, Halcyon G. Skinner, Michael Goggins, Elizabeth M. Jaffee, Charles J. Yeo, John L. Cameron, Scott E. Kern and Ralph H. Hruban
Cancer Res June 1 2001 (61) (11) 4320-4324;
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