Distinct patterns of structural and numerical chromosomal instability characterize sporadic ovarian cancer.
Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN), which can generate both numerical [(N)-CIN] and structural chromosomal instability [(S)-CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels of both (N)-CIN and (S)-CIN. Six tumors had a near-diploid chromosome number, two were near-tetraploid, and two were near-triploid. (N)-CIN levels increased as a function of overall tumor genomic content, with near-diploid tumors exhibiting numerical instability indices ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S)-CIN was generally more evident in the diploid tumors compared with the near-tetraploid tumors. To determine whether the associated chromosomal constitution and/or ploidy changes were influenced by mitotic segregation errors, centrosome analyses were performed on all 10 tumors. The near-diploid tumors, with the lowest numerical change, were observed to possess fewer cells with centrosome abnormalities (5.5% to 14.0%), whereas the near-tetraploid tumors possessed much higher levels of (N)-CIN and were characterized by a trend of elevating percentages of cells with abnormal centrosomes (16.0% to 20.5%). These observations suggest that two distinct processes governing genome stability may be disrupted in ovarian cancer: those that impact on numerical segregation and ploidy of chromosomes and those that affect the fidelity of DNA repair and lead to structural aberrations.
Bayani
Jane
J
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Paderova
Jana
J
Murphy
Joan
J
Rosen
Barry
B
Zielenska
Maria
M
Squire
Jeremy A
JA
D000782:Aneuploidy; D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002503:Centromere / Q000235:genetics / Q000473:pathology; D043171:Chromosomal Instability / Q000502:physiology*; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D002888:Chromosomes, Human, Pair 19; D002892:Chromosomes, Human, Pair 22; D005260:Female; D006801:Humans; D007621:Karyotyping; D010051:Ovarian Neoplasms / Q000235:genetics*