Christacos Nicole C, Quade Bradley J, Dal Cin Paola, Morton Cynthia C
Department of Obstetrics, Gynecology, and Reproductive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Genes Chromosomes Cancer. 2006 Mar;45(3):304-12. doi: 10.1002/gcc.20291.
Cytogenetic analysis of uterine leiomyomata (UL) shows that about 40% of these benign tumors have simple, clonal chromosomal rearrangements. In contrast, their presumed malignant counterpart, leiomyosarcomas (LMSs), typically has complex numerical and structural abnormalities. Several variants of benign uterine smooth-muscle tumors are defined by histologic phenotypes intermediate between typical UL and LMS, and currently, little is known about their cytogenetic and molecular genetic features. From a subset of more than 800 karyotyped ULs, we identified a group of nine cases exhibiting near-diploid karyotypes with loss of almost the entire short (p) arm of chromosome 1 [i.e., del(1)(p11p36)]. Loss of 1p was often associated with other aberrations, particularly loss of chromosomes 19 and/or 22. Of eight UL for which the histologic diagnosis was known, four were diagnosed as cellular UL; one displayed both hypercellularity and nuclear atypia. Loss of heterozygosity (LOH) analysis for chromosomal regions 1p36.23 and 1p21.1 demonstrated allelic loss for either a portion or the majority of 1p in 5 of 10 additional archival UL diagnosed with either cellular or atypical histology. RNA from two UL with loss of 1p was profiled using Affymetrix GeneChips, and those profiles were compared to our previously reported smooth-muscle tumor expression profile. The transcriptional profiles of tumors with 1p deletion were more similar to those of leiomyosarcoma than to profiles of myometrium and UL, as determined by hierarchical cluster analysis. Comparison of the transcriptional profiles for UL with and without 1p-- revealed 53 genes with differential regulation. Loss of 1p appears to define a subgroup of UL distinct from those previously recognized. Furthermore, 1p-- appears to be associated with a specific histologic phenotype. The similarity between the transcriptional profiles of LMS and UL with 1p-- suggests the possibility of a common pathogenetic mechanism.
子宫平滑肌瘤（UL）的细胞遗传学分析表明，约40%的这类良性肿瘤具有简单的克隆性染色体重排。相比之下，其推测的恶性对应物，即平滑肌肉瘤（LMS），通常具有复杂的数目和结构异常。良性子宫平滑肌肿瘤的几种变体由介于典型UL和LMS之间的组织学表型定义，目前，对其细胞遗传学和分子遗传学特征知之甚少。从800多个已核型分析的UL子集中，我们鉴定出一组9例病例，其核型接近二倍体，几乎整个1号染色体短（p）臂缺失[即del(1)(p11p36)]。1p缺失常与其他畸变相关，特别是19号和/或22号染色体缺失。在已知组织学诊断的8例UL中，4例被诊断为细胞性UL；1例表现出细胞增多和核异型性。对10例经细胞性或非典型组织学诊断的存档UL进行1p36.23和1p21.1染色体区域杂合性缺失（LOH）分析，结果显示其中5例1p的部分或大部分存在等位基因缺失。使用Affymetrix基因芯片对2例1p缺失的UL的RNA进行分析，并将这些分析结果与我们之前报道的平滑肌肿瘤表达谱进行比较。通过层次聚类分析确定，1p缺失肿瘤的转录谱与平滑肌肉瘤的转录谱比与子宫肌层和UL的转录谱更相似。对有和无1p缺失的UL的转录谱进行比较，发现53个基因存在差异调控。1p缺失似乎定义了一个与先前认识的UL不同的亚组。此外，1p缺失似乎与一种特定的组织学表型相关。LMS与1p缺失的UL转录谱之间的相似性提示了共同致病机制的可能性。
