Anti-SH3GL2 (aa 64-124) polyclonal antibody

To understand the association of candidate tumour suppressor genes SH3GL2, p16(INK4a), p14(ARF), and p15(INK4b) 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, p16(INK4a), and p14(ARF) showed a higher frequency of overall alterations (60-70%) than in p15(INK4b) (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 p16(INK4a)/p14(ARF) 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 p15(INK4b) have a significant poor patient outcome. The alterations of p16(INK4a), P14(ARF), and p15(INK4b) 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(-)tobaccol(+) (III), and HPV(+)tobacco(+) (IV). Groups III and TV showed a high frequency of p16(INK4a)/P14(ARF)/p15(INK4b) alterations with significant poor patient outcome in comparison to group II. Our findings suggest that deregulation of SH3GL2-associated signalling and p16(INK4a)/p14(ARF)/p15(INK4b)-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 (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Head and neck squamous cell carcinoma (HNSCC) is the most common and fatal cancer type in India with about 30-40% of frequency. Molecular etiologies of the disease include consumption of alcohol, tobacco habit and HPV infection. The lack of understanding in molecular pathogenesis of the disease leads to poor survival of HNSCC patients. Cytogenetic analysis has shown that the chromosomal abnormalities gradually increase with progression of the tumor in a non-random manner. Molecular analysis of-copy number variation, promoter methylation, mutation and expression (gene and protein) revealed identification of some of the candidate tumor suppressor genes located in the chromosomal 3p, 8q, 9p/q, 11q, 13q and 17p etc. regions associated with development of HNSCC. These genes are further seen to control different cellular pathways like-(1) frequent inactivation of SH3GL2 and CDC25A-associated with EGFR homeostasis and de-phosphorylation respectively; (2) Rb and p53 associated pathways in G1-S cell cycle transition; (3) Slit-ROBO associated signaling pathways; (4) PTCH associated Hedgehog signaling; (5) DNA repair pathways like-mismatch and double strand break repair; (6) apoptosis and (7) integrin signaling. Now, systemic approach has been taken to characterize the molecular pathways in this tumor to find out the key regulatory steps for management of the disease.