Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

  title={Characterization of the common fragile site FRA9E and its potential role in ovarian cancer},
  author={Gwen Callahan and Stacy R. Denison and Leslie A Phillips and Viji Shridhar and David I. Smith},
Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human… 

Molecular characterization of the human common fragile site FRA1H

The FRA1H DNA sequence was analyzed to identify coding sequences, the AT content, the type and quantity of the DNA repeats, the CpG islands, the matrix attachment regions, and the number and distribution of high‐flexibility regions and a 120 kb long sequence was identified that may be involved in inducing fragility in the surrounding regions.

Relationship between FRA11F and 11q13 gene amplification in oral cancer

Findings suggest that gene amplification involving chromosomal band 11q13 in OSCC may be initiated by breakage at FRA11F, a nonstaining gaps or breaks in chromosomes that are expressed under conditions inducing replicative stress.

A selected group of large common fragile site genes have decreased expression in oropharyngeal squamous cell carcinomas

The results suggest that this selected group of large genes might serve as potential tumor suppressors involved in the development of OPSCCs, and are located within the two most frequently expressed CFSs.

Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer

Characterization of FRA6E (6q26), the third most frequently observed common fragile site (CFS) in the human population, determined that aphidicolin‐induced instability at FRA6E extends over a very

Common Fragile Sites: Genomic Hotspots of DNA Damage and Carcinogenesis

Recent studies of FATS (for Fragile-site Associated Tumor Suppressor), a new CACG at FRA10F, reveal an active role of this CACGs in regulating DNA damage checkpoints and suppressing tumorigenesis.

Molecular characterization of common fragile sites as a strategy to discover cancer susceptibility genes

The cytogenetic hypothesis that common fragile sites (cFSs) are hotspots of cancer breakpoints is increasingly supported by recent data from whole-genome profiles of different cancers, and emphasis is put on less-studied cFS genes as potential contributors to cancer development.

Short communication Biallelic deletion and loss of expression analysis of genes at FRA2G common fragile site in tumor-derived cell lines

It is found that Burkitt lymphoma-derived cell line DAUDI has a biallelic deletion of eight of the nine analyzed genes, and loss of expression of the DHRS9 gene (alias RDHL), one of the deleted genes in the DAUDi cell line, is observed in MOLT- 14 and Raji cell lines derived from BurkITT lymphoma and from T-cell acute lymphoblastic leukemia.



Molecular characterization of FRAXB and comparative common fragile site instability in cancer cells

The hypothesis that common fragile sites and their associated genes are, in general, unstable in some cancer cells is supported, including FRAXB, which is not associated with any known tumor suppressor genes or activity.

The characterization of the common fragile site FRA16D and its involvement in multiple myeloma translocations.

This work assembled a BAC contig of >1 Mb across the second most active common fragile site, FRA16D (16q23.2), and demonstrated that FRA 16D decondensation/breakage occurs over a region of at least 1 Mb, which is the largest common fragile sites cloned to date.

Characterization of the human TESTIN gene localized in the FRA7G region at 7q31.2.

The findings suggest that TESTIN may represent a candidate tumor suppressor gene at 7q31.2, showing loss of heterozygosity in human malignancies and the genomic structure of the human TESTIN locus was determined and three alternative transcripts were characterized.

Transcriptional profiling reveals that several common fragile‐site genes are downregulated in ovarian cancer

Data is provided to suggest that several of the genes mapped to common fragile sites within CFSs may be inactivated in 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

FISH-based analysis of three overlapping P1 clones reveals that aphidicolin-induced breakage in the FRA7G region occurs over a region of at least 300 Kb in length and there is an association with both spcDNAs and hot-spots for viral integration.

Fish mapping of YAC clones at human chromosomal band 7q31.2: Identification of YACS spanning FRA7G within the common region of LOH in breast and prostate cancer

Several overlapping YAC clones are identified that map precisely to the common region of LOH in breast cancer and prostate cancer, and the MET oncogene is contained within the three YACs that span FRA7G.

FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites.

To the knowledge, this is the first molecular characterization of an in vivo viral integration event within a confirmed fragile site region, supporting previous cytogenetic observations linking viral integration sites and fragile sites.

WWOX: A candidate tumor suppressor gene involved in multiple tumor types

  • A. PaigeK. Taylor J. Watson
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
The homozygous deletion of WWOX exons from ovarian cancer cells and three different tumor cell lines is demonstrated and evidence strengthens the case for WWOX as a tumor suppressor gene in ovarian cancer and other tumor types.

Molecular characterization of a common fragile site (FRA7H) on human chromosome 7 by the cloning of a simian virus 40 integration site.

  • D. MishmarA. Rahat B. Kerem
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
These unusual DNA characteristics are possibly intrinsic properties of common fragile sites that may affect their replication and condensation as well as organization, and may lead to fragility.

Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis.

The FRA16A locus in individuals who do not express the fragile site is not a site of DNA methylation (imprinting), which suggests that the methylation associated with fragile sites may be a consequence and not a cause of their genesis.