Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q.
We have analyzed 30 cases of advanced-stage cervical squamous cell carcinoma (stages IIb-IV) by comparative genomic hybridization (CGH). The most consistent chromosomal gain in the aneuploid tumors was mapped to chromosome arm 3q in 77% of the cases. Acquisition of genetic material also occurred frequently on Iq (47%), 5p (30%), 6p (27%), and 20 (23%). Recurrent losses were mapped on 2q (33%), 3p (50%), 4 (33%), 8p (23%), and 13q (27%). High-level copy number increases were mapped to chromosome 8, chromosome arms 3q, 5p, 8q, 12p, 14q, 17q, 19q, 20p, and 20q, and chromosomal bands 3q26-27, 9p23-24, 11q22-23, and 12p13. In the majority of the cases, the presence of high-risk human papilloma virus genomes was detected. High proliferative activity was accompanied by crude aneuploidy. Increased p21/WAF-I activity, but low or undetectable expression of TP53 were representative for the immunophenotype. This study confirms the importance of a gain of chromosome arm 3q in cervical carcinogenesis and identifies additional, recurrent chromosomal aberrations that are required for progression from stage I tumors to advanced-stage carcinomas.
Heselmeyer
K
K
Diagnostic Development Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD 20892-4470, USA.
Macville
M
M
Schröck
E
E
Blegen
H
H
Hellström
A C
AC
Shah
K
K
Auer
G
G
Ried
T
T
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008875:Middle Aged; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections; D011003:Ploidies; D014412:Tumor Virus Infections; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
D004273:DNA, Neoplasm