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

In a large series of ovarian carcinomas from 244 patients, 134 cases had ch romosome rearrangements. We showed before that the pattern of chromosome br eakpoints involved 21 separate chromosome regions nonrandomly and, in 90% o f cases with breaks, the breakpoints occurred within 13 commonly involved r egions. Log-rank and proportional hazards regression analyses showed that t he aggregate presence of a chromosome breakpoint in any of 21 nonrandomly i nvolved 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 invol ved regions, were not associated with decreased survival. Because many case s had breakpoints in more than one nonrandomly involved region, proportiona l hazards regression was also used to analyze for effects of each nonrandom ly involved region, controlling for effects of other regions. With this app roach, only breakpoints within 1p1 and 3p1 retained independent, deleteriou s effects on survival. Similarly, when nonrandomly involved regions were en tered into a proportional hazards model containing clinical variables assoc iated 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) we re associated with independent, negative effects on survival. These studies demonstrate that chromosome breakpoints within specific, nonrandomly invol ved chromosome regions are associated with impaired survival in ovarian can cers. Regions 1p1 and 3p1 are identified as areas of particular significanc e and are appropriate targets for analytical techniques such as SAGE and mi croarray analysis. Genes Chromosomes Cancer 25:46-52, 1999. (C) 1999 Wiley- Liss, Inc.