Amplification of CyclinL1 in Uterine Cervical Carcinoma Has Prognostic Implications
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Amplification of CyclinL1 in Uterine Cervical
Carcinoma Has Prognostic Implications
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| Creator |
Mitra, Sraboni
Mazumder, Dipanjana Basu, Partha S Mondal, Ranajit Kumar Roy, Anup Roychoudhury, Susanta Panda, Chinmay K |
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| Subject |
Molecular & Human Genetics
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| Description |
The chromosomal 3q25.31 region was consistently amplified in primary cancer of cervix (CACX). CyclinL1 is a
candidate gene of this region and already have been implicated as an oncogene in head and neck cancers. In this
study, we aimed to investigate the involvement of CyclinL1 in cervical carcinogenesis and for this purpose its copy
number variation (CNV) was studied in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN lesions
CyclinL1 was not amplified; however, the amplification frequency was 16% (9/56) in stage I/II tumors which remained
comparable during subsequent stages of tumorigenesis. This implied association of CyclinL1 amplification with
development of early invasiveness. Quantitation of mRNA expression revealed 2.6�1.53-fold overexpression of this
gene in primary CACX. The amplification/copy number gain of CyclinL1 and its mRNA profile were concordant, in
tumors. Immunohistochemical (IHC) analysis in primary CACX, cell lines: SiHa and HeLa revealed intense nuclear
expression of cyclinL1, which was further confirmed by Western blot in the cell lines. However 47% (7/15) CACX
samples expressed high/intermediate level of cyclin L1. Kaplan–Meier survival analysis indicated CyclinL1 amplification
as a determinant of poor patient outcome. Tumor radio-resistance developed as a consequence of CyclinL1
amplification. Cox multivariate analysis revealed that multiparous (�5) CACX patients with amplified CyclinL1 locus
along with advanced tumor stage (III/IV) had worst prognosis. Our data suggest importance of CyclinL1 in cervical
carcinogenesis with its associated pathways viz: pre-mRNA splicing, cell-cycle regulation (G0/G1 and G2/M) being
potential targets of therapeutic interventions in CACX. � 2010 Wiley-Liss, Inc.
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| Publisher |
John Wiley & Sons
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| Date |
2010
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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/86/1/MOLECULAR_CARCINOGENESIS_49(11)_935%2D943;2010[20].pdf
Mitra, Sraboni and Mazumder, Dipanjana and Basu, Partha S and Mondal, Ranajit Kumar and Roy, Anup and Roychoudhury, Susanta and Panda, Chinmay K (2010) Amplification of CyclinL1 in Uterine Cervical Carcinoma Has Prognostic Implications. Molecular Carcinogenesis, 49 (11). pp. 935-943. ISSN 0899-1987 |
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| Relation |
http://dx.doi.org/10.1002/mc.20671
http://www.eprints.iicb.res.in/86/ |
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