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《Chinese Journal of Pathology》 2003-04
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X-chromosome inactivation patterns of different tumor nodules in multiple leiomyomas of uterus

DIAO Xiao-li, SU Qin *, WANG Shu-fang, ZHANG Wei, GONG Li, LIU Jie, FENG Ying-ming. *Department of Pathology, Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi′an, Shaanxi 710038, China  
Objective To describe the relationship among different tumor nodules in multiple leiomyomas of uterus. Methods Genomic DNA was extracted from fresh tissue samples, digested through incubation with methylation-sensitive Hha I or Hpa II, and amplified via PCR for androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism on AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining, the PGK gene products were treated with Bst Ⅺ and resolved on agarose gels. Results 112 cases of leiomyomas and one case of leiomyosarcoma were examined, 89% showing the length polymorphism for AR gene and 30% carring the polymorphic Bst Ⅺ site at PGK locus. Loss of X-chromosome inactivation mosaicism was observed in all the 321 tumor nodules examined from 77 cases, reflecting their clonal cellular composition. The relationship between different nodules was evaluated by their X-chromosome inactivation patterns in the 295 tumor nodules taken from 57 multiple leiomyomas. Similar inactivated alleles were found in all nodules in 30, in most nodules in 7 cases, similar to a multi-nodular leiomyosarcoma, while 20 cases showed near-random distribution of the inactivated alleles in different nodules, indicating their multicentric origins. No relevance was found between this difference and any histopathological parameters including number of mitotic figures and occurrence of bizarre nuclei and degeneration. In addition, an identical mutation and loss of heterozygosity were found at the AR locus in two apparently discrete tumor nodules in one case, providing further evidence for the unicellular origin of these lesions. Conclusions The multi-nodular leiomyomas may be classified into multicentric, unicentric types, as well as a mixed type. It remains to be clarified whether different nodules in the unicentric cases originate from a parent tumor by migration or by spreading.
【Fund】: 国家自然科学基金资助项目 (3 0 1710 5 2 );; 国家回国人员研究启动基金资助项目 (Hg980 0 4);; 陕西省卫生厅科研基金资助项目 (0 2D0 2 )
【CateGory Index】: R737.33
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