Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer. Genes Chromosomes Cancer 2003 Sep;38(1):40-52
Date
07/23/2003Pubmed ID
12874785DOI
10.1002/gcc.10236Scopus ID
2-s2.0-0042522482 (requires institutional sign-in at Scopus site) 124 CitationsAbstract
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 large region (3.6 Mb). Sequence analysis identified eight genes (IGF2R, SLC22A1, SLC22A2, SLC22A3, PLG, LPA, MAP3K4, and PARK2) as mapping within the large FRA6E region. PARK2, the gene associated with autosomal recessive juvenile parkinsonism (ARJP), accounts for more than half of the CFS. Homozygous deletions and large heterozygous deletions have been observed in PARK2 in ARJP patients. RT-PCR analysis of the eight genes localizing to FRA6E indicated that 50% of the genes, including PARK2, were down-regulated in one or more of the primary ovarian tumors analyzed. PARK2 expression was down-regulated in 60.0% of the primary ovarian tumors analyzed. Additionally, we found tumor-specific alternative transcripts of PARK2. Loss of heterozygosity analysis of primary ovarian tumors by use of polymorphic markers in the 6q26 region demonstrated 72% LOH in the center of the PARK2 gene, the highest of any of the markers tested. FRA6E shares many similarities with FRA3B (3p14.2) and FRA16D (16q23.2) in representing a large region of genomic instability and containing an extremely large gene that may play a role in the development of ovarian and many other cancers.
Author List
Denison SR, Callahan G, Becker NA, Phillips LA, Smith DIAuthor
Gwen Lomberk PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Chromosome BreakageChromosome Deletion
Chromosome Fragile Sites
Chromosome Fragility
Chromosome Mapping
Chromosomes, Human, Pair 6
Cloning, Molecular
Female
Humans
Ligases
Loss of Heterozygosity
Ovarian Neoplasms
Parkinson Disease
Parkinsonian Disorders
Reverse Transcriptase Polymerase Chain Reaction
Ubiquitin-Protein Ligases
