Loss of heterozygosity on the long arm of human chromosome 7 in sporadic renal cell carcinomas

Abstract

Cytogenetic and molecular analysis of DNA sequences with highly polymorphic microsatellite markers have implicated allele loss in several chromosomal regions including 3p, 6p, 6q, 8p, 9p, 9q, 11p and 14q in the pathogenesis of sporadic renal cell carcinomas (RCCs). Deletions involving the long arm of chromosome 7 have not been described in RCCs although they have been seen in several other tumor types. However, there have been no detailed analysis of loss of heterozygosity (LOH) of 7q sequences in sporadic RCCs. We therefore studied LOH for DNA sequences on 7q with 10 highly polymorphic markers in 92 matched normal/tumor samples representing sporadic RCCs including papillary, nonpapillary, and oncocytomas in order to determine whether allelic loss could be detected in a tumor type with no visible 7q rearrangements at the cytogenetic level. We found chromosome 7q allele loss in 59 of 92 cases (64%) involving one, two, or more microsatellite markers. The most common allele loss included loci D7S522 (24%) and D7S649 (30%) at 7q31.1-31.2, a region that contains one of the common fragile sites, FRA7G. By comparative multiplex PCR analysis, we detected a homozygous deletion of one marker in the 7q 31.1-31.2 region in one tumor, RC21. These results support the idea that a tumor suppressor gene in 7q31 is involved in the pathogenesis of sporadic renal cell carcinomas.

Caveolin-1 expression in human breast lobular cancer progression

“…These findings have led to the hypothesis that this region encodes a novel tumour suppressor gene. [11][12][13][14][15]28,29 Moreover, the human Cav-1 gene was mapped to the D7S522 region of 7q31. 1,10 suggesting that Cav-1 may indeed represent the tumour suppressor in this fragile genomic region.…”

“…6,[8][9][10] This chromosomal region (D7S522/7q31.1) is a suspected tumour suppressor locus and a common fragile site (known as FRA7G) that is frequently deleted in a number of human cancers. [11][12][13][14][15][16] Thus, Cav-1 may be the as yet unidentified tumour suppressor gene located at the D7S522/7q31.1 locus. [8][9][10] In addition, Cav-1 has demonstrated an important role in mammary gland physiology and morphology.…”

Localization of a novel tumor suppressor gene associated with human oral cancer on chromosome 4q25

“…The deletions of DNA sequences on chromosome 4 were interstitial in most of these tumor samples. No homozygous deletions were found by comparative multiplex PCR analysis which was described by Shridhar et al (1997). Representative autoradiographs of the markers D4S404 and D4S1611 illustrating LOH, and D4S404 and D4S406 illustrating MI are shown in Figure 2.…”

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

“…Consistent with this the chromosomal loci of caveolin-1 and -2 has been recently identified as 7q31.1 (Engelman et al, 1999), a fragile site frequently deleted in a wide spectrum of human cancers that includes cases of sporadic RCC. Such chromosomal rearrangements may result in translocations, deletions or amplification of genes at this locus (Shridhar et al, 1997), although the functional significance of such changes on caveolin in RCC remain to be determined.…”