Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix.
We have chosen tumors of the uterine cervix as a model system to identify chromosomal aberrations that occur during carcinogenesis. A phenotype/genotype correlation was established in defined regions of archived, formalin-fixed, and hematoxylin/eosin-stained tissue sections that were dissected from normal cervical epithelium (n = 3), from mild (n = 4), moderate (n = 6), and severe dysplasias/carcinomas in situ (CIS) (n = 13), and from invasive carcinomas (n = 10) and investigated by comparative genomic hybridization. The same tissues were analyzed for DNA ploidy, proliferative activity, and the presence of human papillomavirus (HPV) sequences. The results show that an increase in proliferative activity and tetraploidization had occurred already in mildly dysplastic lesions. No recurrent chromosomal aberrations were observed in DNA extracted from normal epithelium or from mild and moderate dysplasias, indicating that the tetraploidization precedes the loss or gain of specific chromosomes. A gain of chromosome 3q became visible in one of the severe dysplasias/CIS. Notably, chromosome 3q was overrepresented in 90% of the carcinomas and was also found to have undergone a high-level copy-number increase (amplification). We therefore conclude that the gain of chromosome 3q that occurs in HPV16-infected, aneuploid cells represents a pivotal genetic aberration at the transition from severe dysplasia/CIS to invasive cervical carcinoma.
Heselmeyer
K
K
Diagnostic Development Branch, National Center for Human Genome Research/National Institutes of Health, Bethesda, MD 20892, USA.
Schröck
E
E
du Manoir
S
S
Blegen
H
H
Shah
K
K
Steinbeck
R
R
Auer
G
G
Ried
T
T
D000782:Aneuploidy; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ; D002584:Cervix Uteri / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002893:Chromosomes, Human, Pair 3; D004273:DNA, Neoplasm / Q000235:genetics; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm