SH3GL2 and CDKN2A/2B loci are independently altered in early dysplastic lesions of head and neck: correlation with HPV infection and tobacco habit
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
SH3GL2 and CDKN2A/2B loci are independently altered in
early dysplastic lesions of head and neck: correlation with
HPV infection and tobacco habit
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| Creator |
Ghosh, Amlan
Ghosh, Susmita Maiti, Guru P Sabbir, Mohammed G Alam, Neyaz Sikdar, Nilabja Roy, Bidyut Roychoudhury, Susanta Panda, Chinmay K |
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| Subject |
Molecular & Human Genetics
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| Description |
To understand the association of candidate tumour suppressor genes SH3GL2, p16INK4a ,
p14ARF, and p15INK4b in the pathogenesis of head and neck squamous cell carcinoma
(HNSCC), we studied the deletion, mutation, and methylation of these genes in 61 dysplastic
lesions and 94 HNSCC samples. In mild dysplasia, SH3GL2, p16INK4a, and p14ARF showed
a higher frequency of overall alterations (60–70%) than in p15INK4b (40%). However, in
subsequent stages of tumour progression, the alteration frequency of these genes did not
change significantly. One novel mutation in common exon 2 of p16INK4a/p14ARF and three
in exon 9 of SH3GL2 were seen. Concordance was seen in the expression of these genes with
their molecular alterations. Deletions of INK4A-ARF and p15INK4b have a significant poor
patient outcome. The alterations of p16INK4a , p14ARF, and p15INK4b were positively correlated
with tobacco and inversely with HPV, while SH3GL2 alterations were independent
of these factors. Based on aetiological factors, four tumour subtypes were recognized:
HPV−tobacco− (I), HPV+tobacco− (II), HPV−tobacco+ (III), and HPV+tobacco+ (IV).
Groups III and IV showed a high frequency of p16INK4a/p14ARF /p15INK4b alterations
with significant poor patient outcome in comparison to group II. Our findings suggest
that deregulation of SH3GL2-associated signalling and p16INK4a/p14ARF/p15INK4b-mediated
G1–S/G2–M checkpoints of cell cycle are independent pathways for the development of
early dysplastic lesions of the head and neck.
Copyright 2008 Pathological Society of Great Britain and Ireland. Published by John
Wiley & Sons, Ltd.
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| Publisher |
John Wiley & Sons
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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/219/1/JOURNAL_OF_PATHOLOGY%2C217(3)%2C408%2D419%2C2009[111].pdf
Ghosh, Amlan and Ghosh, Susmita and Maiti, Guru P and Sabbir, Mohammed G and Alam, Neyaz and Sikdar, Nilabja and Roy, Bidyut and Roychoudhury, Susanta and Panda, Chinmay K (2009) SH3GL2 and CDKN2A/2B loci are independently altered in early dysplastic lesions of head and neck: correlation with HPV infection and tobacco habit. The Journal of Pathology, 217 (3). pp. 408-419. ISSN 0022-3417 |
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| Relation |
http://www.eprints.iicb.res.in/219/
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