title: Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata.
abstract: Uterine leiomyomata are thought to be monoclonal neoplasms. Accordingly, investigations of clonality with G6PD isoforms used as a marker for X chromosome inactivation have suggested independent origins for multiple tumors within individual uteri. However, results from a recent study assessing methylation differences between DNA of active and inactive X chromosomes have been interpreted to suggest that multiple tumors may arise from a common precursor. We have examined the clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X-linked androgen receptor gene. As shown by this assay, all informative leiomyomata were monoclonal in origin. In patients with multiple leiomyomata, a random distribution of inactivation between the X homologs was noted, consistent with an independent origin of each tumor. Cytogenetic analysis was also performed on short-term cell cultures of 27 of the 36 tumors. In each of two tumors that had both cells with a clonal karyotypic abnormality and karyotypically normal cells, DNA prepared from short-term cultures showed a monoclonal pattern of X inactivation identical to that of the leiomyoma from which they were derived. These data suggest that karyotypically normal cells present in short-term cultures of uterine leiomyomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aberrations.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: R D
authors.initials: RD
authors.lastname: Mashal
authors.forename: M L
authors.initials: ML
authors.lastname: Fejzo
authors.forename: A J
authors.initials: AJ
authors.lastname: Friedman
authors.forename: N
authors.initials: N
authors.lastname: Mitchner
authors.forename: R A
authors.initials: RA
authors.lastname: Nowak
authors.forename: M S
authors.initials: MS
authors.lastname: Rein
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
authors.forename: J
authors.initials: J
authors.lastname: Sklar
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002869:Chromosome Aberrations; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D007621:Karyotyping; D018231:Leiomyomatosis / Q000235:genetics* / Q000473:pathology; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011944:Receptors, Androgen