Simple tandem repeat allelic deletions confirm the preferential loss of distal chromosome 6q in melanoma

Abstract

Karyotypic analysis, loss of somatic heterozygosity, microcell fusion and cDNA transfection studies have provided compelling evidence that at least one tumour suppressor gene for melanoma resides on chromosome 6. In an attempt to further define the regions to which these putative suppressor genes map, we have carried out loss of heterozygosity (LOH) studies on DNA from 25 fresh melanoma tumours for 9 simple tandem repeat (STR) polymorphism markers spanning chromosome 6. Four samples displayed LOH or homozygosity for all markers studied, indicating that they had lost one homologue of chromosome 6. An additional 3 samples showed LOH for all markers on 6q. Furthermore, 30 melanoma cell lines, for which there were no matching somatic DNA samples, were analyzed for hemizygosity of markers on 6q. One cell line had a homozygous deletion of all markers tested and a further 12 cell lines displayed only one allele for 3 or 4 contiguous markers, indicating that most, if not all of these samples were hemizygous for the region of 6q distal to D6S87. Overall, the rate of LOH on 6q in the 55 melanoma DNAs was 35%, and there were no losses of markers on 6p without concomitant loss of markers on 6q. Two of 5 samples derived from primary melanomas showed LOH, which indicates that LOH for the melanoma suppressor gene on 6q, which maps to a region that contains the SOD2 locus, is a frequent and early event in melanoma tumorigenesis.

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

“…This suggests that its role in tumor suppression is not restricted to tumors of ovarian origin, but may be important for a large variety of di erent cancer types. Indeed, deletions or losses of heterozygosity a ecting chromosome 6 were reported in cancers from a large number of di erent organs including carcinomas of the breast (Devilee et al, 1991;Sheng et al, 1996), endometrium (Tibiletti et al, 1997), and prostate (Cooney et al, 1996), as well as in small cell lung carcinomas (Merlo et al, 1994), lymphomas and leukemias (Gerard et al, 1997;Menasce et al, 1994), and melanomas (Walker et al, 1994).…”

Prognostic significance of allelic losses in primary melanoma

“…Investigations on cutaneous melanoma have demonstrated that multiple genetic abnormalities exist within these tumours (reviewed in Rees and Healy, 1996). Cytogenetic studies have detected gains and losses of genetic material on multiple chromosomes, and subsequent studies on loss of heterozygosity (LOH) have con®rmed the ®nding of frequent allelic loss (Cowan et al, 1988;Dracopoli et al, 1989;Trent et al, 1990;Millikin et al, 1991;Fountain et al, 1992;Isshiki et al, 1993Isshiki et al, , 1994Herbst et al, 1994;Holland et al, 1994;Walker et al, 1994;Healy et al, 1995Healy et al, , 1996aThompson et al, 1995). Recent work has shown that 6q, 9p and 10q are the chromosome arms most frequently lost in this tumour, with evidence that allelic losses on 6q and 10q may be responsible for the malignant phenotype in this neoplasm (Healy et al, 1996a).…”

Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma

“…Chromosome alterations in malignant melanoma most frequently include a variety of nonreciprocal translocations and simple deletions involving chromosome 1 (Trent et al, 1989;Fountain et al, 1990;Thompson et al, 1995), complete or partial loss of the long arm of chromosome 6 (Trent et al, 1989;Fountain et al, 1990) frequent alterations of the short arm of chromosome 9 (Skolnick et al, 1994;Thompson et al, 1995;Kraehn et al, 1995) and 1p11-q22 (Thompson et al, 1995;Kraehn et al, 1995). Evidence of a putative tumor suppressor gene on chromosome 6 has been suggested by cytogenetic observation (Trent et al, 1989;Fountain et al, 1990), by high frequency of loss of heterozygosity (LOH) along 6q (Milliken et al, 1991;Walker et al, 1994) and by studies suggesting that either tumorigenicity or metastasis of melanoma cell lines can be suppressed by the introduction (following micro-cell mediated chromosome transfer) of a normal copy of human chromosome 6 (Trent et al, 1990;You et al, 1995;Ray et al, 1996).…”