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Research Article

Replication Error-positive Samples Found in Pheochromocytomas

NIVES PECINA-SLAUS, TAMARA NIKUSEVA-MARTIC, KORALJKA GALL-TROSELJ, KRESIMIR RADIC and RENO HRASCAN
In Vivo March 2005, 19 (2) 359-365;
NIVES PECINA-SLAUS
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TAMARA NIKUSEVA-MARTIC
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KORALJKA GALL-TROSELJ
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KRESIMIR RADIC
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RENO HRASCAN
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Abstract

Background: Adenomatous polyposis coli, (APC) and E-cadherin (CDH1) tumor suppressor genes were investigated in human pheochromocytoma. Both genes are components of adherens junctions, but are also involved in wnt signalling in which one of the target molecules is c-myc protein. Materials and Methods: Fifteen sporadic pheochromocytomas were tested for gene instability by PCR/loss of heterozygosity. Detection of c-myc protein was performed using immunohistochemistry. Results: One sample with allelic imbalance of the APC gene and one with allelic imbalance of the CDH1 gene were found. Interestingly, another type of genomic instability was detected - replication error-positive samples (RER+). Four out of 13 heterozygous samples were RER-positive (30.8%). The instability is the result of impaired cellular mismatch repair. Immunohistochemistry showed increased levels of c-myc in comparison to normal adrenal tissue. Conclusion: Our results suggest that microsatellite genetic instabilities of the E-cadherin gene have a role in pheochromocytoma development and progression. Detected instability indicates that mismatch repair may be targeted in pheochromocytoma. Increased expression of c-myc protein as well as allelic imbalances of APC and CDH 1 genes suggest that the wnt signalling pathway may have a role in this malignancy.

Keywords:
  • Pheochromocytoma
  • APC gene
  • E-cadherin gene
  • loss of heterozygosity
  • replication error

Footnotes

    • Received September 1, 2004.
    • Revision received November 24, 2004.
    • Accepted December 27, 2004.
  • Copyright © 2005 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved
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March-April 2005
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Replication Error-positive Samples Found in Pheochromocytomas
NIVES PECINA-SLAUS, TAMARA NIKUSEVA-MARTIC, KORALJKA GALL-TROSELJ, KRESIMIR RADIC, RENO HRASCAN
In Vivo Mar 2005, 19 (2) 359-365;

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Replication Error-positive Samples Found in Pheochromocytomas
NIVES PECINA-SLAUS, TAMARA NIKUSEVA-MARTIC, KORALJKA GALL-TROSELJ, KRESIMIR RADIC, RENO HRASCAN
In Vivo Mar 2005, 19 (2) 359-365;
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