Chromosome abnormalities in ovarian adenocarcinoma: I. nonrandom chromosome abnormalities from 244 cases

Abstract

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. Genes Chromosomes Cancer 25:290–300, 1999. © 1999 Wiley‐Liss, Inc.

Chromosomal Abnormalities in Endometrial and Ovarian Carcinomas

“…The THY1 gene was mapped to the 11q23~24, which has been identified by both Taetle et al [1] and Garba et al [22] to have a high incidence of LOH in ovarian cancer. The location of the THY1 gene at this region makes this a suitable tumor suppressor gene for ovarian cancer.…”

“…Our cytogenetic findings provide strong evidence that multiple genetic lesions are associated with the development of endometrial cancers, and that deletions of 3p13, p21, p23, q21 and q25 may play a specific role in the pathogenesis of such cancers. Chromosomal abnormalities have been known to occur in malignant tumors for a long time [1][2][3][4][5]. This study adds little to the understanding of the field of ovarian cancer cytogenetics; the results for endometrial cancer are more novel and could be improved by analyses of more cases.…”

“…Most of these neoplasms are associated with chromosomal abnormalities and show a constellation of rearrangements such as translocations, deletions, and inversions [1][2][3][4][5]. However, understanding of the molecular genetic and cyto genetic changes associated with ovarian tumor development and disease progression has been limited because of the extreme complexity of the abnormalities [2].…”

“…Chromosomal deletions in cancer cells are often found to contain tumor suppressor genes [7,8]. Structural rearrangements of chromosome arms 1p, 1q, 3p, 3q, 6q, 7p, 9q, 11p, 11q, 17q, 19p, and 19q were identified in ovarian tumors [1][2][3]5]. Taken together, these findings suggest that certain chromosomal abnormalities are important in the pathogenesis of ovarian and endometrial cancers.…”

Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation

“…Published karyotypic analyses have tended to include epithelial ovarian cancers of all histological subtypes and have shown frequent abnormalities of chromosomes 1, 3, 6, 11, 17 and 19, with less frequent abnormalities of chromosomes 2, 4, 5, 9 and 21 (Gallion et al, 1990;Taetle et al, 1999;Roberts and Tattersall, 1990). The development of improved molecular techniques including the use of polymorphic genetic markers has provided more precise ways to identify these genetic abnormalities.…”