Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma.
BACKGROUND
Carcinoma of uterine cervix is the second most common cancers among women worldwide. Combined radiation and chemotherapy is the choice of treatment for advanced stages of the disease. The prognosis is poor, with a five-year survival rate ranging from about 20-65%, depending on stage of the disease. Therefore, genetic characterization is essential for understanding the biology and clinical heterogeneity in cervical cancer (CC).


METHODS
We used a genome-wide screening method--comparative genomic hybridization (CGH) to identify DNA copy number changes in 77 patients with cervical cancer. We applied categorical and survival analyses to analyze whether chromosomal changes were related to clinico-pathologic characteristics and patients survival.


RESULTS
The CGH analysis revealed a loss of 2q33-q37 (57.1%), gain of 3q (54.5%) and chromosomal amplifications (20.77%) as frequent genetic changes. A total of 15 amplified chromosomal sites were detected in 16 cases that include 1p31, 2q32, 7q22, 8q21.2-q24, 9p22, 10q21, 10q24, 11q13, 11q21, 12q15, 14q12, 17p11.2, 17q22, 18p11.2, and 19q13.1. Recurrent amplified sites were noted at 11q13, 11q21, and 19q13.1. The genomic alterations were further evaluated for prognostic significance in CC patients, and we did not find any correlation with a number of clinical or histological parameters. The tumors harboring HPV18 exhibited higher genomic instability compared to tumors with HPV 16.


CONCLUSIONS
This study demonstrated that 2q33-q37 deletions, 3q gains and chromosomal amplifications as characteristic changes in invasive CC. These genetic alterations will aid in the identification of novel tumor suppressor gene(s) at 2q33-q37 and oncogenes at amplified chromosomal sites. Molecular characterization of these chromosomal changes utilizing the current genomic technologies will provide new insights into the biology and clinical behavior of CC.
Rao
Pulivarthi H
PH
Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA. prao@bcm.tmc.edu
Arias-Pulido
Hugo
H
Lu
Xin-Yan
XY
Harris
Charles P
CP
Vargas
Hernan
H
Zhang
Fang F
FF
Narayan
Gopeshwar
G
Schneider
Achim
A
Terry
Mary Beth
MB
Murty
Vundavalli V V S
VV
D000230:Adenocarcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005784:Gene Amplification; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods; D027383:Papillomaviridae / Q000302:isolation & purification; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology