Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix.
Genome-wide microarray-based comparative genomic hybridization (array CGH) was used to identify common chromosomal alterations involved in cervical carcinogenesis as a first step towards the discovery of novel biomarkers. The genomic profiles of nine squamous cell carcinomas (SCCs) and seven adenocarcinomas (AdCAs), as well as four human papillomavirus (HPV)-immortalized keratinocyte cell lines, were assessed. On a genome-wide scale, SCCs showed significantly more gains than AdCAs. More specifically, there was a striking and highly significant difference between the two histological types for gain at 3q12.1-28, which was predominantly observed in SCC. Other frequent alterations included gains of 1q21.1-31.1 and 20q11.21-13.33, and losses of 11q22.3-25 and 13q14.3-21.33. Subsequent FISH analysis for hTR, located at 3q26, confirmed the presence of 3q gain in SCCs and HPV-immortalized cell lines. Fine mapping of chromosome 20q using multiplex ligation-dependent probe amplification (MLPA) showed copy number increases for a number of genes located at 20q11-q12, including DNMT3B and TOP1. For DNMT3B, this correlated with elevated mRNA expression in 79% of cases. In conclusion, the assessment of frequent genomic alterations resulted in the identification of potential novel biomarkers, which may ultimately enable a better risk stratification of high-risk (hr)-HPV-positive women.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
S M
SM
Wilting
P J F
PJ
Snijders
G A
GA
Meijer
B
B
Ylstra
P R L A
PR
van den Ijssel
A M
AM
Snijders
D G
DG
Albertson
J
J
Coffa
J P
JP
Schouten
M A
MA
van de Wiel
C J L M
CJ
Meijer
R D M
RD
Steenbergen
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002874:Chromosome Mapping / Q000379:methods; D002877:Chromosomes, Human / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D027383:Papillomaviridae; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000097584:DNA Methyltransferase 3B