title: Mutation analysis of CDP, TP53, and KRAS in uterine leiomyomas.
abstract: Leiomyomas are the most common gynecologic tumors in women, but very little is known about their molecular pathology. We used single-stranded conformational polymorphism/heteroduplex analysis to analyze 42 unselected uterine leiomyomas for somatic mutations in all coding exons of the gene encoding CCAAT displacement protein (CDP), as well as exons 5-8 of TP53 and codons 1-36 and 38-80 of KRAS. No somatic mutations were identified in either TP53 or KRAS, indicating that disregulation of these genes is not required for leiomyomas development. Aberrant band shifts were identified in CDP, but these were all germline nonpathogenic variants that have been reported previously. There is good functional and genetic evidence indicating that CDP is a leiomyoma suppressor, but our data suggested that somatic mutations in this gene were rare in unselected uterine leiomyomas. It is possible that CDP belongs to a class of tumor suppressor in which loss of only one copy of the gene, either by genetic or epigenetic mechanisms, is sufficient to allow tumor growth.
authors.affiliation: Department of Obstetrics and Gynaecology, Gynaecological Cancer Research Centre, University of Melbourne, Royal Women's Hospital, Carlton, Victoria, Australia.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Patrikis
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Bryan
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Thomas
authors.forename: Greg E
authors.initials: GE
authors.lastname: Rice
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quinn
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baker
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D011905:Genes, ras; D018398:Homeodomain Proteins; D006801:Humans; D007889:Leiomyoma / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: C080632:CUX1 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53