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Molecular alterations at chromosome 9p21 in melanocytic naevi and melanoma

Sini, Maria Cristina and Manca, A. and Cossu, Annalisa and Budroni, Marilena and Botti, Gerardo and Ascierto, Paolo Antonio and Cremona, Francesco and Muggiano, Antonio and D'Atri, Stefania and Casula, Milena and Baldinu, Paola and Palomba, Grazia and Lissia, Amelia and Tanda, Francesco and Palmieri, Giuseppe (2008) Molecular alterations at chromosome 9p21 in melanocytic naevi and melanoma. British Journal of Dermatology, Vol. 158 (2), p. 243-250. eISSN 1365-2133. Article.

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DOI: 10.1111/j.1365-2133.2007.08310.x

Abstract

Background The chromosome 9p21 and its CDKN locus, with the p16 tumour suppressor gene (CDKN2A), are recognized as the genomic regions involved in the pathogenesis of melanoma. Objectives To elucidate further the role of such regions during the different phases of melanocytic tumorigenesis. Methods Tissue sections from naevi, primary and metastatic melanomas were investigated by fluorescence in situ hybridization for allelic loss at the 9p21 chromosome and by immunochemistry for p16CDKN2A expression. Results Dysplastic naevi and primary or secondary melanomas were found to carry hemizygous deletions within the entire 9p21 region at similar frequencies (varying from 55% to 62%). Allelic deletion spanning the CDKN locus was observed at significantly increased rates moving from early (7%) to advanced (28%) primary melanomas and to secondary melanoma lesions (37%) (P = 0·018). Also, inactivation of the p16 gene (CDKN2A) was absent in naevi and present at steadily increasing rates moving from primary melanomas (7% early lesions to 17% advanced lesions) to melanoma metastases (62%) (P = 0·004). Conclusions Our findings indicate that, in a model of sequential accumulation of genetic alterations, 9p21 deletions may play a role in melanocytic transformation and tumour initiation whereas rearrangements at the CDKN locus, and p16 gene (CDKN2A) inactivation may contribute to tumour progression.

Item Type:Article
ID Code:1816
Status:Published
Refereed:Yes
Uncontrolled Keywords:Chromosome 9p21, FISH analysis, melanomagenesis, p16CDKN2A protein expression
Subjects:Area 06 - Scienze mediche > MED/08 Anatomia patologica
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL1, Sassari > Centro multizonale di osservazione epidemiologica
001 Università di Sassari > 03 Istituti > Anatomia patologica
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
Publisher:Blackwell / Wiley
eISSN:1365-2133
Copyright Holders:© 2007 The Authors, Journal Compilation © 2007 British Association of Dermatologists
Deposited On:18 Aug 2009 10:06

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