Chromosome abnormalities in ovarian adenocarcinoma: II. prognostic impact of nonrandom chromosome abnormalities in 244 cases

Abstract

In a large series of ovarian carcinomas from 244 patients, 134 cases had chromosome rearrangements. We showed before that the pattern of chromosome breakpoints involved 21 separate chromosome regions nonrandomly and, in 90% of cases with breaks, the breakpoints occurred within 13 commonly involved regions. Log-rank and proportional hazards regression analyses showed that the aggregate presence of a chromosome breakpoint in any of 21 nonrandomly involved regions and breaks in 9 distinct regions (1p1, 1q2, 1p3, 3p1, 6p2, 11p1, 11q1, 12q2, and 13p1) were associated with reduced patient survival. Breakpoints in other areas of the genome, including other nonrandomly involved regions, were not associated with decreased survival. Because many cases had breakpoints in more than one nonrandomly involved region, proportional hazards regression was also used to analyze for effects of each nonrandomly involved region, controlling for effects of other regions. With this approach, only breakpoints within 1p1 and 3p1 retained independent, deleterious effects on survival. Similarly, when nonrandomly involved regions were entered into a proportional hazards model containing clinical variables associated with altered patient survival (tumor grade, tumor stage, and residual disease > 1 cm after resection), only 1p1 (P = 0.007) and 3p1 (P = 0.04) were associated with independent, negative effects on survival. These studies demonstrate that chromosome breakpoints within specific, nonrandomly involved chromosome regions are associated with impaired survival in ovarian cancers. Regions 1p1 and 3p1 are identified as areas of particular significance and are appropriate targets for analytical techniques such as SAGE and microarray analysis.

Expression Microarrays

“…More evident were concordant CGH and SKY aberrations leading to losses distal to 3p21 and gains of 3q and of the region 8q23-q24 arising as a consequence of unbalanced structural rearrangements. In addition, other regions of rearrangement on chromosomes 1, 7, 12, 13, and 19 previously identified by G-banded chromosomal analysis (12,13) were also noted. One-third more structural chromosomal aberrations were identified in the endometrioid tumors than the serous tumors.…”

“…Many chromosomal translocations were centromeric or pericentromeric, suggesting the involvement of repetitive centromeric sequences or Alu repeats that may facilitate rearrangements leading to chromosomal imbalance (52). Chromosomal breakage at 1p1* and 3q* occur in ovarian cancer (5,7,11) and confers a poor outcome (13). Ovarian cancer often presents in more than one site or has metastasized at the time of surgery.…”

“…12 Internet address: http://www.utoronto.ca/cancyto/OVCA2001CR/. 13 Internet address: http://www.utoronto.ca/cancyto/. 14 On the basis of the CGH findings, it is likely that the deleted region of 8p arises as a result of a complex translocation involving 19 and 13 (inverted DAPI banding suggests that this segment derives from 8p).…”

“…A cytogenetic survey of 244 ovarian carcinomas identified a clustering of chromosomal translocation breakpoints occurring in the regions 1p1*, 1q1*, 1p2*, 1q2*, 1p3*, 1q3, 3p1*, 1q4*, 6q1*, 6p2, 6q2, 7p1, 7p2*, 11p1*, 11q2*, 12p1, 12q2*, 13p1, and 19q1 [where the asterisk (*) denotes the most commonly involved regions of chromosomal rearrangement] (12)(13)(14). The presence of translocations in the regions shown above was associated with reduced patient survival.…”

Copy Number Changes in 1q21.3 and 1q23.3 have Different Clinical Relevance in Ovarian Tumors

“…Cytogenetic studies and spectral karyotyping have shown chromosome 1 to be frequently involved in rearrangements in ovarian tumors [1][2][3][4][5]. However, specific genes in chromosome 1, of importance for ovarian carcinogenesis, are still not identified.…”