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  • Title: Use of X-chromosome inactivation pattern to determine the clonal origins of uterine leiomyoma and leiomyosarcoma.
    Author: Zhang P, Zhang C, Hao J, Sung CJ, Quddus MR, Steinhoff MM, Lawrence WD.
    Journal: Hum Pathol; 2006 Oct; 37(10):1350-6. PubMed ID: 16949924.
    Abstract:
    Uterine leiomyomas (LMs) and leiomyosarcomas (LMSs), both of smooth muscle origin, sometimes coexist in the same uterus. Little genetic evidence exists concerning the developmental relationship between LM and LMS. Using the X-chromosome inactivation pattern of the human androgen receptor gene, we examined the clonality of LM and LMS. Of the 24 patients with LM, 21 had multiple neoplasms; all were clonal and individual LMs derived from separate clones. Of the 20 patients with LMS, 6 exhibited multiple tumors in the uterus, and 4 of these individuals also harbored coexisting uterine LMs. We found all LMSs to be clonal. Separate tumors showed identical pattern of X inactivation in 4 patients, and in 2 other individuals, multiple LMSs developed from independent clones. Among the 4 patients with LMS and coexisting LM, 3 showed the same pattern of X inactivation in LMS and the adjacent LM. In 2 of the 3 patients, the tumor also exhibited a morphological transition between benign cells in LM and malignant cells in LMS, supporting the possibility of transformation from LM to LMS. One patient displayed different clones in LMS and the coexisting LM, indicating their independent origins. We conclude that (i) both LM and LMS are clonal; (ii) different nodules in multiple LM are of independent origins; (iii) multiple lesions of LMS may be either monoclonal or multiclonal; (iv) most LMSs are solitary lesions and are most likely de novo, but an individual LM may undergo "malignant transformation" to a LMS; and (v) some LMSs and coexisting LMs are of independent origins.
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