Taetle R, Aickin M, Yang J M, Panda L, Emerson J, Roe D, Adair L, Thompson F, Liu Y, Wisner L, Davis J R, Trent J, Alberts D S
Department of Medicine, University of Arizona, Tucson, Arizona Cancer Center, 85724, USA.
Genes Chromosomes Cancer. 1999 Jul;25(3):290-300.
Cytogenetics provides important insights into the molecular pathogenesis of human cancers. Although extensive data exist on recurring cytogenetic abnormalities in hematologic cancers, data on individual solid tumor types remain limited. Previous studies of ovarian carcinoma indicated the presence of multiple, complex clonal chromosome abnormalities. Cytogenetics remains one of a few techniques capable of detecting these multiple, simultaneously occurring genetic abnormalities. We describe cytogenetic abnormalities from a series of 244 primary ovarian cancer specimens referred to a single institution. A total of 201/244 cases had fully characterized clonal chromosome abnormalities, of which 134 showed clonal chromosome breakpoints. We used a novel statistical technique to detect nonrandom chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints was detected at regions 1p1*, 1q1*, 1p2*, 1q2*, 1p3*, 1q3, 3p1*, 1q4*, 6q1*, 6p2, 6q2, 7p1*, 7q1, 7p2*, 11p1*, 11q1, 11q2*, 12p1, 12q2*, 13p1, and 19q1. Simultaneous occurrence of multiple abnormalities was common. However, 120/134 cases had breakpoints at one or more of 13 commonly involved regions (*), suggesting a hierarchy of genetic abnormalities. Among clinical and tumor variables that predict patient survival, tumor grade was significantly associated with the presence of chromosome breakpoints. In additional studies, we show that nonrandom chromosome abnormalities are associated with impaired survival in ovarian cancer and that specific, nonrandomly involved chromosome regions retain significant effects on survival when analyses are controlled for important clinical variables. Additional specific chromosome abnormalities in this series are described, including chromosome gains and losses in near-diploid cases and homogeneously staining regions. These results suggest that recurring, nonrandom chromosome abnormalities are important in the pathogenesis and/or progression of ovarian cancers, and target areas of the genome for molecular genetic studies.
细胞遗传学为深入了解人类癌症的分子发病机制提供了重要线索。尽管关于血液系统癌症中反复出现的细胞遗传学异常已有大量数据，但关于个别实体瘤类型的数据仍然有限。先前对卵巢癌的研究表明存在多种复杂的克隆性染色体异常。细胞遗传学仍然是能够检测这些多种同时发生的基因异常的少数技术之一。我们描述了来自一家机构的244例原发性卵巢癌标本的细胞遗传学异常情况。共有201/244例病例具有完全特征化的克隆性染色体异常，其中134例显示出克隆性染色体断点。我们使用一种新颖的统计技术在染色体区域水平检测非随机染色体断点。在1p1*、1q1*、1p2*、1q2*、1p3*、1q3、3p1*、1q4*、6q1*、6p2、6q2、7p1*、7q1、7p2*、11p1*、11q1、11q2*、12p1、12q2*、13p1和19q1区域检测到染色体断点的非随机出现。多种异常同时出现很常见。然而，120/134例病例在13个常见受累区域（*）中的一个或多个区域存在断点，提示基因异常存在层次结构。在预测患者生存的临床和肿瘤变量中，肿瘤分级与染色体断点的存在显著相关。在进一步的研究中，我们表明非随机染色体异常与卵巢癌患者生存受损相关，并且当分析控制了重要临床变量时，特定的、非随机受累的染色体区域对生存仍有显著影响。本系列中还描述了其他特定的染色体异常，包括近二倍体病例中的染色体增减和均匀染色区。这些结果表明，反复出现的非随机染色体异常在卵巢癌的发病机制和/或进展中很重要，并为分子遗传学研究确定了基因组的目标区域。
