The Characterization of the Common Fragile Site FRA16D and Its Involvement in Multiple Myeloma Translocations

Krummel, Kurt A.; Roberts, Lewis R.; Kawakami, Masaki; Glover, Thomas W.; Smith, Jeremy C.

doi:10.1006/geno.2000.6321

Cited by 86 publications

(85 citation statements)

References 31 publications

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“…To date, the molecular location and analysis of six CFSs have been reported in the literature (Wilke et al, 1996a;Huang et al, 1998;Mishmar et al, 1998;Krummel et al, 2000;Mangelsdorf et al, 2000;Paige et al, 2000;Arlt et al, 2002;Morelli et al, 2002). This analysis along with our initial report (Thorland et al, 2000) has determined the molecular localization of eight additional CFSs.…”

Section: Discussionsupporting

confidence: 55%

“…The 87 CFSs are distributed throughout the genome. To date, six aphidicolin-sensitive CFSs have been cloned and characterized: FRA3B, FRA7G, FRA7H, FRA16D, FRAXB, and FRA6F (Wilke et al, 1996a;Huang et al, 1998;Mishmar et al, 1998;Krummel et al, 2000;Mangelsdorf et al, 2000;Paige et al, 2000;Arlt et al, 2002;Morelli et al, 2002). The mechanistic reason for the instability of these sites is still unclear, but it is likely different from that of the RFSs since no unstable repeat sequences have been shown to be associated with CFSs.…”

Section: Introductionmentioning

confidence: 99%

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Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Thorland¹,

Myers²,

et al. 2003

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The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. HPV integration into the genome of infected cervical cells is temporally associated with the acquisition of the malignant phenotype. A relationship between the sites of HPV integration in cervical cancer and the position of the common fragile sites (CFSs) has been observed at both the cytogenetic and molecular levels. To further explore this relationship at the molecular level, we used RS-PCR to rapidly isolate cellular sequences flanking the sites of HPV16 integration in 26 primary cervical tumors. Human bacterial artificial chromosome clones were isolated based on these flanking sequences and used as probes for fluorescence in situ hybridization on aphidicolin-stimulated metaphases. Our data demonstrate that 11/23 HPV16 integrations in cervical tumors occurred within CFSs (Po0.001). In addition, we show that deletions and complex rearrangements frequently occur in the cellular sequences targeted by the integrations and that integrations cluster in FRA13C (13q22), FRA3B (3p14.2), and FRA17B (17q23). Finally, our data suggest that cellular genes, such as Notch 1, are disrupted by the HPV16 integrations, which may contribute to the malignant phenotype.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Thorland¹,

Myers²,

et al. 2003

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“…Moreover, homozygous deletions at 16q23.2 have been identi®ed in malignant ovarian ascites, in an ovarian tumor cell line, a colon carcinoma cell line, two small cell lung cancer cell lines, and a gastric adenocarcinoma cell line (Watson et al, 1999;Mangelsdorf et al, 2000;Paige et al, 2000Paige et al, , 2001. A common region of homozygous deletion of 270 kb has been sequenced, coinciding with the fragile site FRA16D Mangelsdorf et al, 2000;Krummel et al, 2000). These results strongly suggest the presence of a suppressor gene involved in tumor progression on 16q23.…”

Section: Discussionmentioning

confidence: 99%

Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors

et al. 2002

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The presence of putative tumor-suppressor genes on chromosome 16q23.2-24.1 has been suggested by LOH analysis in several cancer types. This region overlaps with the fragile site FRA16D and the region of homozygous deletions found in several cancer types. The candidate gene WWOX/FOR has been mapped within this region. The mouse homologue of the WWOX protein has been de®ned as an apoptogenic protein and an essential partner of p53 in cell death, supporting WWOX as a tumor suppressor gene candidate. We performed an expression study of the WWOX/FOR gene in a series of human breast tumors and breast cancer cell lines, and detected reduced expression of the WWOX/ FOR transcript in a series of breast cancer cells. Furthermore, identi®cation of two distinct alternative WWOX transcripts expressed at high levels in human tumors suggests an involvement of the WWOX gene in breast cancer progression.

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“…In two (OCI-My5; JJN-3) of three MM cell lines from which we have cloned the breakpoints from both derivatives, we ®nd evidence of large deletions of 16q23 sequences, whereas we found only very small deletions of 4p16 and 11q13 for the three t(4;14) and one t(11;14) translocations in which sequences from both derivatives were obtained. Perhaps the translocation-associated deletions are related to the occurrence of the breakpoints within the fragile site (FRA16D) located in this region (Bednarek et al, 2000;Krummel et al, 2000;Nakazawa et al, 2000;Ried et al, 2000). The breakpoints on 16q23 also emphasize another feature that is common to the IgH translocations in MM, i.e., they are dispersed over a great distance centromeric to a dysregulated oncogene: 50 ± 100 kb from FGFR3 (4p16), 12 ± 330 kb from cyclin D1 (11q13); and 550 ± 1350 kb from c-maf (16q23).…”

Section: Anatomy Of Igh Translocations In MMmentioning

confidence: 99%

Chromosome translocations in multiple myeloma

2001

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The Characterization of the Common Fragile Site FRA16D and Its Involvement in Multiple Myeloma Translocations

Cited by 86 publications

References 31 publications

Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Common fragile sites are preferential targets for HPV16 integrations in cervical tumors

Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors

Chromosome translocations in multiple myeloma

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