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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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Title SH3GL2 and CDKN2A/2B loci are independently altered in
early dysplastic lesions of head and neck: correlation with
HPV infection and tobacco habit
 
Creator Ghosh, Amlan
Ghosh, Susmita
Maiti, Guru P
Sabbir, Mohammed G
Alam, Neyaz
Sikdar, Nilabja
Roy, Bidyut
Roychoudhury, Susanta
Panda, Chinmay K
 
Subject Molecular & Human Genetics
 
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.
 
Publisher John Wiley & Sons
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
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
 
Relation http://www.eprints.iicb.res.in/219/