Genomic alterations in uterine leiomyosarcomas: Potential markers for clinical diagnosis and prognosis

Genomic alterations were analyzed in 21 uterine leiomyosarcomas (ULMSs) by comparative genomic hybridization. DNA copy number changes were detected in all 21 tumors. The most frequent losses were 13q (16/21 = 76%), 10q (13/21 = 62%), 16q (8/21 = 38%), 12p (7/21 = 33%), and 2p(9/21 = 43%). The most c ommon gains were 17p(8/21 = 38%), Xp (7/21 = 33%), and 1q (7/21 = 33%). Hig h-copy-number gains (ratio > 1.5) were identified in Xp, Iq, and 17p. Loss of 13q was identified in both low-grade and high-grade tumors. Inactivation of a tumor suppressor gene in 13q may be an early event in the development of leiomyosarcomas. Loss of 10q, 2p, and 12p and gains of Iq as well as 17 p were frequently found in high-grade tumors and recurrent tumors. Inactiva tion of tumor suppressor genes and activation of oncogenes in these regions may be associated with a more aggressive behavior of ULMS. Patients with o nly loss of 13q and without the other alterations listed above had longer s urvival times. Gains of Xp, 17p, and Iq and losses of 13q, 10q, 16q, 12p, a nd 2p have been reported in extra-uterine leiomyosarcomas. Our findings ind icate that the pathogenesis of uterine leiomyosarcomas and extra-uterine le iomyosarcomas follows the same genetic pathways. (C) 2001 Wiley-Liss, Inc.