15 research outputs found
Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck
<p>Abstract</p> <p>Background</p> <p>It is well known that a persistent infection with high-risk human papillomavirus (hrHPV) is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs). The latter differ from hrHPV-negative HNSCCs at the clinical and molecular level.</p> <p>Methods</p> <p>To determine whether hrHPV-associated SCCs arising from different organs have specific chromosomal alterations in common, we compared genome-wide chromosomal profiles of 10 CxSCCs (all hrHPV-positive) with 12 hrHPV-positive HNSCCs and 30 hrHPV-negative HNSCCs. Potential organ-specific alterations and alterations shared by SCCs in general were investigated as well.</p> <p>Results</p> <p>Unsupervised hierarchical clustering resulted in one mainly hrHPV-positive and one mainly hrHPV-negative cluster. Interestingly, loss at 13q and gain at 20q were frequent in HPV-positive carcinomas of both origins, but uncommon in hrHPV-negative HNSCCs, indicating that these alterations are associated with hrHPV-mediated carcinogenesis. Within the group of hrHPV-positive carcinomas, HNSCCs more frequently showed gains of multiple regions at 8q whereas CxSCCs more often showed loss at 17p. Finally, gains at 3q24-29 and losses at 11q22.3-25 were frequent (>50%) in all sample groups.</p> <p>Conclusion</p> <p>In this study hrHPV-specific, organ-specific, and pan-SCC chromosomal alterations were identified. The existence of hrHPV-specific alterations in SCCs of different anatomical origin, suggests that these alterations are crucial for hrHPV-mediated carcinogenesis.</p
Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection
A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors
10.1038/onc.2010.576Oncogene30161923-1935ONCN
Hypoxia-induced 26S proteasome dysfunction increases immunogenicity of mesenchymal stem cells
The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity
Deletions in Chromosome 4 Differentially Associated With the Development of Cervical Cancer: Evidence of Slit2 as a Candidate Tumor Suppressor Gene
The aim of this study was to locate the candidate
tumor suppressor genes (TSGs) loci in the chromosomal
4p15-16, 4q22-23 and 4q34-35 regions associated
with the development of uterine cervical carcinoma
(CA-CX). Deletion mapping of the regions by microsatellite
markers identified six discrete areas with high frequency
of deletions, viz. 4p16.2 (D1: 40%), 4p15.31 (D2:
35–38%), 4p15.2 (D3: 37–40%), 4q22.2 (D4: 34%),
4q34.2-34.3 (D5: 37–59%) and 4q35.1 (D6: 40–50%).
Significant correlation was noted among the deleted
regions D1, D2 and D3. The deletions in D1, D2, D5 and
D6 regions are suggested to be associated with the cervical
intraepithelial neoplasia (CIN), and deletions in the D2,
D3, D5 and D6 regions seems to be associated with progression
of CA-CX. The deletions in the D2 and D6
regions showed significant prognostic implications
(P = 0.001; 0.02). The expression of the candidate TSG
SLIT2 mapped to D2 region gradually reduced from normal cervix uteri fi CIN fi CA-CX. SLIT2 promoter
hypermethylation was seen in 28% CIN samples and significantly
increased with tumor progression (P = 0.04).
Significant correlation was seen between SLIT2 deletion
and its promoter methylation (P = 0.001), indicating that
both these phenomena could occur simultaneously to
inactivate this gene. Immunohistochemical analysis
showed reduced expression of SLIT2 in cervical lesions
and CA-CX cell lines. Although no mutation was detected
in the SLIT2 promoter region (–432 to + 55 bp), CC and
AA haplotypes were seen in –227 and –195 positions,
respectively. Thus, it indicates that inactivation of SLIT2-
ROBO1 signaling pathway may have an important role in
CA-CX development