Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization

Abstract

Uterine leiomyomas are the most prevalent tumor type in women of reproductive age and are the most common reason for hysterectomies. Although uterine leiomyomas are considered to be benign, they are a major public health concern for women. In contrast, leiomyosarcomas are rare but highly malignant uterine tumors. They may arise in uteri with preexisting leiomyomas and histologically sometimes resemble leiomyomas, thus causing controversy about whether leiomyosarcomas arise within leiomyomas. In this study, we used comparative genomic hybridization (CGH) to identify genetic alterations unique to each tumor type and alterations that are common between the two tumors. We analyzed 14 cases of uterine leiomyomas and eight cases of uterine leiomyosarcomas. Only two of the 14 leiomyomas exhibited genetic alterations, and those were restricted to gains on chromosomes 14 and 19 and losses on chromosomes 1 and 4. In addition, 68 leiomyomas were examined for loss of heterozygosity on chromosomes 1 and 4, and only three tumors exhibited any losses. In contrast, all eight leiomyosarcomas showed gains and losses of DNA by CGH, and in many cases multiple changes were observed. The most commonly observed genetic aberration, occurring in five tumors, was gains on both arms of chromosome 1, suggesting that this chromosome contains loci involved in the development of leiomyosarcoma. Our results do not provide evidence for the progression from benign leiomyoma to malignant leiomyosarcoma. Moreover, the large number of random chromosomal alterations in the leiomyosarcomas suggests that increased genetic instability plays a role in the formation of these tumors.

Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors

“…Furthermore, when we performed the hierarchical cluster analysis, these tumors branched together even in smaller sub-clusters indicating that these histologically different entities cannot be distinguished based on copy number profiling. In concordance with the literature, leiomyosarcomas typically demonstrated the highest frequency of copy number alterations, 19,29,46 whereas leiomyomas showed a low number of copy number alterations with a few cases (20%) lacking any gains or losses. Interestingly, all cases of leiomyomas with bizarre nuclei and leiomyosarcomas showed a high number of copy number alterations involving nearly all chromosomes.…”

Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?

“…Gains/losses were identified in several regions, with the most common copy number gains in both UPS and LMS affecting 1p36. 33 The overall gains/losses are in accordance with studies that have applied cytogenetics and fluorescence in situ hybridization and showed extensive genetic alterations with recurrent numerical as well as structural aberrations, including losses of 1p36, 1q42-qter, 2p15-pter, 3p21-p23, 8p21-pter, 10q23-qter, 11q23-qter, 13q12-q13, 13q32-qter, and 18q11, and gains of 1q12-q31, in LMS. [30][31][32] CGH has also been applied to LMS 33 with the most frequent losses affecting 2p, 10q, 11q, and 13q, and the most common gains encompassing 1q, 5p, 8q, 17p, and Xp.…”

Leiomyosarcomas and Most Malignant Fibrous Histiocytomas Share Very Similar Comparative Genomic Hybridization Imbalances: An Analysis of a Series of 27 Leiomyosarcomas

“…LMS are much more common in women than men, even for nonuterine locations. Until now, few cytogenetic or molecular data were available for LMS (Mandahl et al, 2000), and only a few series were analyzed by comparative genomic hybridization (CGH) (El-Rifai et al, 1998;Otano-Joos et al, 1998;Packenham et al, 1997;Parente et al, 1999). In this study, we analyzed a series of 27 LMS by immunohistochemistry and CGH.…”