Deletions in Chromosome 4 Differentially Associated With the Development of Cervical Cancer: Evidence of Slit2 as a Candidate Tumor Suppressor Gene
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Deletions in Chromosome 4 Differentially Associated
With the Development of Cervical Cancer: Evidence of Slit2
as a Candidate Tumor Suppressor Gene
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| Creator |
Singh, Ratnesh Kumar
Indra, Dipanjana Mitra, Sraboni Mondal, Ranajit Kumar Basu, Partha Sarathi Roy, Anup Roychoudhury, Susanta Panda, Chinmay Kumar |
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| Subject |
Molecular & Human Genetics
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| Description |
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.
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| Date |
2007
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/306/1/HUMAN_GENETICS%2C_122(1)%2C_71%2D81[58].pdf
Singh, Ratnesh Kumar and Indra, Dipanjana and Mitra, Sraboni and Mondal, Ranajit Kumar and Basu, Partha Sarathi and Roy, Anup and Roychoudhury, Susanta and Panda, Chinmay Kumar (2007) Deletions in Chromosome 4 Differentially Associated With the Development of Cervical Cancer: Evidence of Slit2 as a Candidate Tumor Suppressor Gene. Hum Genet, 122 (1). pp. 71-81. |
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| Relation |
http://dx.doi.org/10.1007/s00439-007-0375-6
http://www.eprints.iicb.res.in/306/ |
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