IngentaConnect RASSF1A promoter methylation and 3p21.3 loss of heterozygosity ar...

Authors: Pizzi, S¹; Azzoni, C¹; Bottarelli, L¹; Campanini, N¹; D'Adda, T¹; Pasquali, C²; Rossi, G³; Rindi, G¹; Bordi, C¹

Source: The Journal of Pathology, Volume 206, Number 4, August 2005 , pp. 409-416(8)

Publisher: John Wiley & Sons, Ltd.

Abstract:

The Ras-association domain family 1A (RASSF1A) tumour suppressor gene is inactivated in a variety of solid tumours, usually by epigenetic silencing of the promoter and/or allelic loss of its locus at 3p21.3. RASSF1A induces cell cycle arrest through inhibition of cyclin D1 accumulation. In this work, 62 endocrine tumours from different sites in the gut were investigated for methylation of the RASSF1A promoter using the polymerase chain reaction, the presence of 3p21.3 deletions by loss of heterozygosity analysis, and cyclin D1 expression by immunohistochemistry. Methylation was found in 20/62 (32%) cases and was restricted to foregut tumours; deletion at 3p21.3 was found in 15/58 (26%) informative cases and restricted to malignant foregut tumours; cyclin D1 hyperexpression was found in 31/58 (53%) cases and correlated with RASSF1A methylation. Our data suggest that RASSF1A is involved in the development of endocrine tumours derived from the foregut only, and that the presence of both RASSF1A methylation and 3p21.3 deletion is associated with malignancy. These results may provide a rationale for foregut-targeted therapy for aggressive endocrine carcinomas entailing the use of demethylating agents. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: endocrine tumours; gut; RASSF1A; methylation; 3p21; cyclin D1

Document Type: Research article

DOI: 10.1002/path.1784

Affiliations: 1: Department of Pathology and Laboratory Medicine, University of Parma, Parma, Italy 2: Department of Medical and Surgical Sciences, University of Padua, Padua, Italy 3: Department of Pathologic Anatomy and Legal Medicine, University of Modena and Reggio Emilia, Modena, Italy

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$40.19 plus tax Refund Policy

RASSF1A promoter methylation and 3p21.3 loss of heterozygosity are features of foregut, but not midgut and hindgut, malignant endocrine tumours