Packenham J P, du Manoir S, Schrock E, Risinger J I, Dixon D, Denz D N, Evans J A, Berchuck A, Barrett J C, Devereux T R, Ried T
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Mol Carcinog. 1997 Aug;19(4):273-9. doi: 10.1002/(sici)1098-2744(199708)19:4<273::aid-mc9>3.0.co;2-d.
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.
子宫平滑肌瘤是育龄女性中最常见的肿瘤类型，也是子宫切除术最常见的原因。尽管子宫平滑肌瘤被认为是良性的，但它们仍是女性主要的公共卫生问题。相比之下，平滑肌肉瘤是罕见但高度恶性的子宫肿瘤。它们可能发生于已有平滑肌瘤的子宫，在组织学上有时与平滑肌瘤相似，因此引发了关于平滑肌肉瘤是否起源于平滑肌瘤的争议。在本研究中，我们使用比较基因组杂交（CGH）来识别每种肿瘤类型特有的基因改变以及两种肿瘤共有的改变。我们分析了14例子宫平滑肌瘤和8例子宫平滑肌肉瘤。14例平滑肌瘤中只有2例表现出基因改变，且仅限于14号和19号染色体的增加以及1号和4号染色体的缺失。此外，对68例平滑肌瘤进行了1号和4号染色体杂合性缺失检测，只有3例肿瘤表现出任何缺失。相比之下，所有8例平滑肌肉瘤通过CGH均显示出DNA的增加和缺失，并且在许多情况下观察到多种改变。最常见的基因畸变发生在5例肿瘤中，是1号染色体双臂增加，这表明该染色体包含参与平滑肌肉瘤发生发展的基因座。我们的结果并未提供从良性平滑肌瘤进展为恶性平滑肌肉瘤的证据。此外，平滑肌肉瘤中大量随机的染色体改变表明遗传不稳定性增加在这些肿瘤的形成中起作用。
