Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis

The aim of our study, was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF. CDC25A, SCOTIN, RASSFIA anti CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions anti 116 squamous cell carcinoma of head and neck. both deletion and promoter methylation have been seen in these genes except for CDC25A anti SCOTIN where no methylation has been detected. The alteration of LIMDI was highest (50%) in the mild dysplastic lesions and did not change significantly during progression of tumor indicating its association with this stage of the disease. It was evident that alterations of LTF, CDC25A and CACNA2D2 were associated with development of moderate dysplastic lesions, while alterations in RASSFIA and CACNA2D2 were needed for progression. Novel somatic mutations were seen in exon 1 of LIMDI (7%). intron 3/exon4 splice,junction of LTF (2%) and exon 7 of cdc25A (10%). Quantitative RT-PCR analysis revealed mean reduced expression of the genes in the order: LTF (67.6 +/- 16.8) > LIMDI (53.2 +/- 20.1) > CACNA2D2 (23.7 +/- 7.1) > RASSFIA (15.1 +/- 5.6) > CDC25A (5.3 +/- 2.3) > SCOTIN (0.58 +/- 0.54). Immunohistochemical analysis of CDC25A showed its localization both in cytoplasm and nucleus in primary lesions and oral cancer cell lines. In absence of HPN infection, LTF and RASSFIA alterations jointly have adverse impact on survival of tobacco addicted patients. Thus, our data suggested that multiple candidate TSGs in the chromosomal 3p21.31 region were differentially associated with the early dysplastic lesions of head anti neck. (C) 2008 Wiley-Liss, Inc.