title: Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer.
abstract: It has been proposed that the frequent loss of heterozygosity (LOH) of an             entire chromosome 17 contig in epithelial ovarian cancers (EOC) is the consequence             of the inactivation of multiple tumour suppressor genes on this chromosome. We             report the characterization of a 453 Kb 17q25 locus shown previously to exhibit             a high frequency of LOH in EOC samples. LOH analysis further defined the minimal             region of deletion to a 65 Kb interval flanked by D17S2239 and D17S2244, which             contains RHBDF2, CYGB and PRCD as tumour suppressor gene candidates. Tissue specific             expression excluded PRCD as a candidate. RHBDF2 was expressed at low levels in             the majority of benign and low malignant potential (LMP) tumours, and in a subset             of malignant ovarian tumour samples, as compared with primary cultures of normal             ovarian surface epithelial cell (NOSE) samples. CYGB was expressed at low levels             in the majority of LMP and malignant samples compared with benign and NOSE samples.             In contrast to CYGB expression, RHBDF2 was expressed at low or undetectable levels             in EOC cell lines exhibiting tumourigenic characteristics and up-regulated in             a genetically modified EOC cell line rendered non-tumourigenic. DNA sequence analysis             identified variants but no apparent deleterious mutations in either gene. Methylation-specific             PCR analysis suggested that promoter methylation of CYGB but not RHBDF2 occurred             in 6 of 31 malignant samples. The results combined suggest that RHBDF2 and CYGB             may play distinctive roles in ovarian cancer and could be added to the growing             roster of chromosome 17 genes implicated in this disease.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec,                     Canada.
authors.forename: Paulina M
authors.initials: PM
authors.lastname: Wojnarowicz
authors.forename: Diane M
authors.initials: DM
authors.lastname: Provencher
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
mesh_terms: D000595:Amino Acid Sequence; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017124:Conserved Sequence; D000078842:Cytoglobin; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D056726:Genetic Association Studies; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014158:Transcription, Genetic
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D005914:Globins