The most common fragile site in man is 3p14

Smeets, Dominique; Scheres, J. M. J. C.; Hustinx, T. W. J.

doi:10.1007/bf00291880

Cited by 92 publications

(16 citation statements)

References 32 publications

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“…Detailed analysis of the most common fragile site in the human genome, FRA3B in 3p14.2, has revealed frequent breakpoints in this region in cancers, even those with no visible cytogenetic alterations. The FRA7G fragile site, however, has not been characterized in as great detail as FRA3B (Paradee et al, 1995;Wang et al, 1993;Smeets et Kovacs et al, 1988). We have recently shown a clustering of breakpoints in the FRA3B region in pancreatic adenocarcinomas (Shridhar et al, 1996) similar to the observations reported here.…”

Section: Resultssupporting

confidence: 85%

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

et al. 1997

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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.

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Section: Resultssupporting

confidence: 85%

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

et al. 1997

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“…However, whether or not fragile sites play a causative role in these structural chromosome alterations has yet to be determined. FRA3B, at chromosome band 3p14.2, is the most highly inducible fragile site in the human genome (Smeets et al, 1986). The constitutive familial renal cell carcinoma-associated translocation t(3;8)(p14.2;q24) (hRCC) (Cohen et al, 1979) was localized immediately centromeric of FRA3B (Paradee et al, 1995;Boldog et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

et al. 1998

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FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identi®ed putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in dierent tumors. Using a high density of PCR ampli®able markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply re¯ect instability of the FRA3B region during tumor progression.

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“…The proposed most unstable site was found at BAC 14 (RP11-48E21), which contains exon 5 with the start codon of the FHIT gene , making it temping to speculate that deletions in exon 5 may account for reduced expression of the FHIT proteins seen in DLBCL cases (Chen et al, 2004). This frequent region of loss also matches a human common fragile site, FRA3B (Smeets et al, 1986). FRA3B is the most highly fragile site in the human genome, in which unstable sequences with repeats and transposons are included (Huebner and Croce, 2001).…”

Section: Discussionmentioning

confidence: 99%

Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma

et al. 2004

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Deletions of the 3p arm have been detected in various solid tumors, but no study to date has investigated this deletion in diffuse large B-cell lymphoma (DLBCL). Recently, we demonstrated that 3p14.2 was deleted in approximately 30% of DLBCL cases by use of a genome-wide arraycomparative genomic hybridization (CGH). For a more detailed examination of the genomic losses at 3p14.2, here we made use of contig BAC array for 3p14.2, and found that 12 DLBCL samples displayed losses. All of the deleted regions were located within the fragile histidine triad (FHIT) gene, and the most frequent region of loss was mapped to 0.4 Mbp of the region encompassing the introns 4 and 5 and exon 5 of the FHIT gene. Concomitant analysis of transcripts showed that the FHIT gene was aberrantly transcribed in 31% of the DLBCL samples examined and that the lost exons of the aberrant transcripts were correlated with genomic deletions. These findings indicate that (1) loss of genomic material at 3q14.2 is responsible for exon losses of the FHIT gene, and (2) genomic loss of the FHIT gene is one of the causes of the generation of aberrant transcripts.

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The most common fragile site in man is 3p14

Cited by 92 publications

References 32 publications

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

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

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma

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