Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer

Shridhar, Viji; Rivard, Sylvie; Wang, Xiaohong; Shridhar, Ravi; Paisley, Christa; Mullins, Chadwick; Beirnat, Laura; Dugan, Michael C.; Sarkar, Fazlul H.; Miller, Orlando J.; Vaitkevicius, Vainutis K.; Smith, Jeremy C.

doi:10.1038/sj.onc.1201054

Cited by 23 publications

(24 citation statements)

References 14 publications

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“…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. We also observed a dramatic clustering of breakpoints in 3p14.2 with frequent multiple interstitial deletions in RCCs (Shridhar et al, 1997).…”

Section: Resultssupporting

confidence: 88%

“…The biological signi®cance of at least some fragile sites is that they might predispose chromosomes to breakage which would then result in translocations, deletions, or even ampli®cations that could play a role in tumor development. For example, we have demonstrated that a high percentage of both pancreatic adenocarcinomas (Shridhar et al, 1996) and sporadic RCCs (Shridhar et al, 1997) have breakpoints in FRA3B, the most common fragile site in the human genome.…”

Section: Introductionmentioning

confidence: 99%

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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: 88%

Section: Introductionmentioning

confidence: 99%

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

et al. 1997

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“…The clinical signi®cance of fragile sites may be the role they play in chromosomal breakage and deletion during cancer development. We have demonstrated that a high percentage of both pancreatic adenocarcinomas (Shridhar et al, 1996) and sporadic RCCs (Shridhar et al, 1997) have breakpoints in FRA3B, one of the most common aphidicolininducible fragile sites in the human genome (Wang et al, 1993). The LOH data in this study indicates that the region with the second highest heterozygous loss on 6q contains the FRA6E common fragile site.…”

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confidence: 78%

A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer

et al. 1999

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Detailed deletion mapping of chromosome 6q sequences in invasive ovarian tumors have implicated several broad regions involving 6q14 ± 16, 6q21 ± 23, 6q25 ± 26, and the telomeric portion in band 6q27 as regions of frequent loss in this malignancy. In order to de®ne regions of loss involved in the development of ovarian cancer, we used 23 polymorphic markers on 6q to examine allelic loss in 25 high-grade, late stage ovarian tumors. Four nonoverlapping deletion regions were observed: (1) at 6q21 ± 22.3 (D6S301-D6S292); (2) within a 1 cM region at 23.2 ± 23.3 between markers D6S978-D6S1637 (at D6S311); (3) at 6q26 (between markers D6S411-D6S1277) and (4) at 6q27 with the markers D6S297 and D6S193. The highest region of loss was observed with marker D6S311 (lost in 17 of 19 informative cases, 89%) in 6q23.3, followed by D6S977 and D6S1637 (71 and 55%, respectively). The average fractional allele loss in the high-grade tumors was around 35%. Previous reports have shown 6q27 as the region of most frequent loss in invasive ovarian cancer. However, our results indicate a novel region in 6q23.3 (spanning less than 500 Kb distance between the markers) with the highest loss, implicating this region of chromosome 6q to harbor a putative tumor suppressor gene involved in the development of invasive epithelial ovarian cancer.

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“…The analysis of the sequence for much of FRA3B, the most active of the common fragile sites, has not revealed why the FRA3B region is so unstable. However, the molecular characterization of FRA3B has demonstrated that cancer breakpoints and rearrangements do indeed occur right within the FRA3B region at the molecular level (Boldog et al, 1997;Shridhar et al, 1996Shridhar et al, , 1997. We were therefore interested in analysing another common fragile site to determine if a comparison between dierent fragile sites would give insights into their mechanism of instability and also to determine if the position of cancer breakpoints at another fragile site coincided with the precise location of that fragile site.…”

Section: Discussionmentioning

confidence: 99%

FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites

Huang

Qian

Proffit³

et al. 1998

Oncogene

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FRA7G is an aphidicolin-inducible common fragile site at human chromosomal band 7q31.2. This region is frequently altered in a number of dierent tumor types including prostate, breast, and ovarian cancer. It has also been hypothesized that this region contains an important tumor suppressor gene which is mutated during the development of these cancers or an oncogene which is ampli®ed. We previously used a FISH-based approach to isolate YAC clones which spanned FRA7G. In this report, we describe the isolation and restriction endonuclease mapping of three overlapping P1 clones which cover FRA7G and the region frequently altered in the dierent cancers. FISH-based analysis of these clones reveals that aphidicolin-induced breakage in the FRA7G region occurs over a region of at least 300 Kb in length. We have also localized a previously sequenced BAC clone to this region. The sequence obtained from this clone reveals the presence of an endogenous retroviral sequence (HERV-H) in the midst of the FRA7G region as well as sequences with homology to small polydispersed circular DNAs (spcDNAs). Thus for the ®rst two cloned common fragile sites, FRA7G and FRA3B, there is an association with both spcDNAs and hot-spots for viral integration.

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Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer

Cited by 23 publications

References 14 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

A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer

FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites

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