© Kamla-Raj 2003 KEY WORDS Head and neck squamous cell carcinoma; chromosome 3; tumor suppressor gene(s); loss of heterozygosity; microsatellite size alteration. ABSTRACT Detailed deletion mapping was done in the chromosomal 3p21.2-22 and 3p12-13 regions, showing high deletions in our previous study, using 13 highly polymorphic microsatellite markers in 25 primary head and neck squamous cell carcinoma (HNSCC) to narrow down the candidate tumor suppressor genes’ (TSGs) loci. Deletions in the different regions of chr.3p were seen to increase significantly with the progression of the clinical stages as detected by the fractional regional loss (FRL) index analysis. Five discrete areas with the following order of deletion frequency i.e. D3: 3p21.31 > D2: 3p21.32 > D1: 3p21.33 > D4: 3p21.2-21.1 > D5: 3p12.1, had been identified. Among these regions, the onset of deletions during progression of the tumor i.e. from stage I to stage IV, was suggested to occur in the following order i.e. D3 ! D1& D2 ! D4 & D5. The deletion in the D5 region was significantly associated with the progression of the clinical stages. Microsatellite size alterations (MAs) were seen to be high in and around the highly deleted regions. Also loss of normal copy / interstitial alterations of chr.3 in the late stages of the tumor as well as rare biallelic alterations around the highly deleted regions were seen in our samples. The Human Papilloma Virus (HPV) infection was found to be associated with the MAs in D3 region, whereas nodal involvement of the tumor was correlated with the deletions in D1, D2, D4 and D5. Thus, this study indicates that multiple tumor suppressor genes (TSGs) may be present in chr.3p whose differential deletions are associated with the development of HNSCC. INTRODUCTION The incidence of HNSCC tumors is fourth Multiple Deletions in Chromosome 3p are Associated with the Development of Head and Neck Squamous Cell Carcinoma Suman Bhusan Chakraborty 1 , Md. Golam Sabbir 1 , Anup Roy 2 , Arunava Sengupta 3 and Chinmay Kumar Panda 1 1. Department of Oncogene Regulation, Chittaranjan National Cancer institute, 37 S.P. Mukherjee Road, Kolkata 700026, West Bengal, India 2. Department of Pathology, Medical College and Hospital, Kolkata 700073, India 3. Cancer Centre and Welfare Home, Kolkata 700 063, West Bengal India Int J Hum Genet, 3(2): 79-87 (2003) for men and sixth for women in the world (Parkin et al. 1993). In India, about 100,000 individuals suffer from the disease at any given time (Jayanth et al. 1991). Several etiological factors particularly tobacco / alcohol consumption and HPV infection are shown to be linked with the disease (Wu et al. 1994; Gillison et al. 1999). Among the HPVs, the high risk HPV-16 and 18 are most prevalent in the HNSCC tumors (Gillison et al. 2000). But the molecular genetic events associated with the initiation and progression of the disease, are poorly understood. The karyotypes of HNSCC tumors are complex and the chromosomal aberrations have been shown to increase during progression of the tumor (Dasgupta et al. 2002). Among the chromosomal alterations the nonrandom deletions in several chromosomal regions have been suggested to play major role in the development of this tumor (Dasgupta et al. 2002). In a microcell hybrid system, it has been shown that the normal chr.3 could suppress the tumorigenecity of oral cancer cell lines indicating the presence of at least one tumor suppressor gene in this chromosome (Dasgupta et al. 2002). In a preliminary HNSCC progression model the deletion in the chr.3p has been suggested to be necessary for the development of dysplastic head and neck lesions (Califano et al. 1996), while others have reported that deletions in chr.3p might be the late event in this tumorigenesis (El- Naggar et al. 1995). Also there is ambiguity in identification of common deleted regions in chr.3p among the different investigators (Wu et al. 1994; Maestro et al. 1993; Field et al. 1994; Roz et al. 1996; Partridge et al. 1996). In our previous study of HNSCC tumors from Indian patients two broad chromosomal regions 3p12-13 (9.7cM) and 3p21.2-22 (16.1cM) with Corresponding Author: Dr. Chinmay K. Panda, Depart- ment of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata- 700 026, West Bengal India. Phone: 91-33-2474-3922, Fax: 91-33-2475 7606, E-Mail: ckpanda@vsnl.net