Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic
lesions of head and neck: clinical and prognostic implications
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| Creator |
Ghosh, Susmita
Ghosh, Amlan Maiti, Guru Prasad Alam, Neyaz Roy, Anup Roychoudhury, Susanta Panda, Chinmay Kumar |
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| Subject |
Molecular & Human Genetics
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| Description |
Deletion of chromosomal 3p12.3 was suggested
to be associated with dysplastic lesions of head and neck.
This region harbors two candidate tumor suppressors
ROBO1/DUTT1, ROBO2 and two non-coding RNAs (ncRNAs)
located at intron 2 of ROBO1/DUTT1. Aim of this
study is to understand the role of these genes in development
of head and neck squamous cell carcinoma. A collection
of 72 dysplastic lesions and 116 HNSCC samples and
two oral cancer cell lines were analyzed for ROBO1/
DUTT1 and ROBO2 deletion and promoter methylation.
ROBO1/DUTT1, ROBO2 and two ncRNAs mRNA expression
were analyzed by Q-PCR. Immunohistochemical
analysis of ROBO1/DUTT1 and ROBO2 was performed.
Alterations of these genes were correlated with diVerent clinicopathological parameters. High frequency of molecular
alterations (deletion/methylation) was seen in ROBO1/
DUTT1 than ROBO2. In mild dysplastic lesions both of
these genes showed high molecular alterations and
remained more or less constant in subsequent stages. QPCR
analysis showed reduced expression of these genes
and the two ncRNAs. In vitro demethylation experiment by
5-aza-dC showed upregulation of ROBO1/DUTT1 and
ROBO2 while the expression of the ncRNAs remained
unchanged. Immunohistochemical analysis of ROBO1/
DUTT1 and ROBO2 showed concordance with their
mRNA expression and molecular alterations. Poor patients’
outcome was predicted in the cases with alteration of
ROBO1/DUTT1 along with tobacco addiction and nodal
involvement. Our data suggests (a) ROBO1/DUTT1 and the
ncRNAs are transcribed from diVerent promoters, and (b)
inactivation of ROBO1/DUTT1 could be used as molecular
signature for early detection and prognosis of the head and
neck cancer.
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| Publisher |
Springer Verlag
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| Date |
2009
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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/182/1/HUMAN_GENETICS%2C_125(2)%2C189%2D198%2C2009[99].pdf
Ghosh, Susmita and Ghosh, Amlan and Maiti, Guru Prasad and Alam, Neyaz and Roy, Anup and Roychoudhury, Susanta and Panda, Chinmay Kumar (2009) Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications. Human Genetics, 125 (2). pp. 189-198. |
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| Relation |
http://dx.doi.org/10.1007/s00439-008-0610-9
http://www.eprints.iicb.res.in/182/ |
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