Deletions of the region 17p11-13 in advanced melanoma revealed by cytogenetic analysis and fluorescence in situ hybridization

Abstract

Malignant melanoma (MM) is a common cancer amongCaucasians and has shown a deplorable increase in incidence rates during recent decades. Early diagnosis -and consequently early surgical excision -has been greatly improved, leading to an average 5-year survival rate of up to 80%. Therefore, stable incident death rates of MM could be observed. However, the prognosis of metastatic MM still remains poor, with a long-term survival rate of about 20% in stage III patients (Balch et al, 1992;Johnson et al, 1995).Cytogenetic analyses of cell lines derived from MM have been reported for more than 20 years (Chen et al, 1973). The data obtained are quite complex and not always unambiguous. However, the non-random involvement of chromosomes 1, 6, 7 and 9 has been published repeatedly (Chen et al, 1973;Koprowski et al, 1985;Heim et al, 1988;Trent at al, 1990;Balch et al, 1992). Deletions or loss of function of the p53 tumour-suppressor gene (p53-TSG) have been found in roughly 50% of all malignant tumours . Mutations of the p53-TSG have been found to be characteristic for carcinogenes and biochemical mechanisms responsible for genetic lesions in DNA that cause cancer (Harris et al, 1993). Loss of function of p53 has been reported for colon, oesophageal squamous cell, pancreatic and hepatic carcinoma and other malignant tumours of the brain, lung, breast and ovary (Levine, 1993). Despite numerous studies, no clear information on the role of p53 in MM is available to date (Stretch et al, 1991;Akslen et al, 1992;Catresana et al, 1993;Piepkorn, 1994;Kanoko et al, 1995;Poremba et al, 1995;Saez-Santamaría et al, 1995;Talve et al, 1996). The majority of cultured MM cell lines is described to express p53 protein as assessed by monoclonal antibody binding. Point mutations in the p53 coding sequence (usually cytosine to thymidine) have been found in 30% of cases (Piepkorn, 1994). Stretch et al report that 73% of primary and 93% of metastatic melanomas express mutant p53 protein (Stretch et al, 1991). However, there are also reports describing a reduced p53 expression in metastatic MM compared with primary lesions (Catresana et al, 1993).To investigate the role of p53-TSG in metastatic MM, we analysed 11 metastatic MM derived from 11 patients cytogenetically by chromosome banding techniques and FISH after shortterm culture. In addition, paraffin-embedded tissues of 9 of the 11 MM were examined immunohistochemically using DO-7, an antibody reacting with both wild-type and mutant p53 protein. MATERIAL AND METHODS MaterialEleven surgically removed, histologically confirmed metastatic MM (ME 1 to ME 11) from 11 patients were minced with scissors and prepared for short-term culture by standard methods (Pederson et al, 1986). Patients' data are briefly described in Table 1. For preparing MM specimens for cytogenetic investigation, collagenase (Worthington Biochemical Corporation, NJ, USA) 200 U ml -1 was used over night.The next day, cells were washed three times to start cultivation in a collagenase-free medium with RPMI-1640 medium (Sera-l...

Longitudinal Study of Recurrent Metastatic Melanoma Cell Lines Underscores the Individuality of Cancer Biology

“…1a ) ( Jonsson et al, 2007 ; Roschke et al, 2003 ; Spivey et al, 2012 ; Thompson et al, 1995 ). Also, at the individual gene level, most genes were affected by copy number gains and losses in accordance with others’ reports ( Grafstrom et al, 2005 ; Jonsson et al, 2007 ; Okamoto et al, 1999 ; Pirker et al, 2003 ; Shi et al, 2012 ) ( Fig. 1b , see full data set in Table S2 ).…”

The <i>TP53</i> Tumor Suppressor Gene and Melanoma Tumorigenesis: Is There a Relationship?

“…In 1998, Park et al [35] found allelic loss in DN but not in BN. In 1999, Okamoto et al [36] reported deletions in the 17p13 region in melanomas ( fig. 1, table 2).…”