Association of FANCC and PTCH1 with the Development of Early Dysplastic Lesions of the Head and Neck

• Published in: Annals of surgical oncology 2012-07, Vol.19 (Suppl 3), p.528-538
• Main Authors: Ghosh, Amlan, Ghosh, Susmita, Maiti, Guru Prasad, Mukherjee, Sudeshna, Mukherjee, Nupur, Chakraborty, Jayanta, Roy, Anup, Roychoudhury, Susanta, Panda, C. K.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Case-Control Studies; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Chromosomes, Human, Pair 9; Confidence Intervals; DNA, Viral - isolation & purification; Fanconi Anemia Complementation Group C Protein - genetics; Female; Gene Expression; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - virology; Homeodomain Proteins - genetics; Human papillomavirus 16; Human papillomavirus 18; Humans; Male; Medicine; Medicine & Public Health; Methylation; Middle Aged; Odds Ratio; Oncology; Patched Receptors; Patched-1 Receptor; Promoter Regions, Genetic; Receptors, Cell Surface - genetics; RNA, Messenger; Sequence Deletion; Surgery; Surgical Oncology; Translational Research and Biomarkers; Xeroderma Pigmentosum Group A Protein - genetics; Young Adult
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-011-1991-x

Background Alteration of chromosome 9q22.3 region is an early and frequent event in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to understand the association of candidate tumor suppressor genes PHF2, FANCC, PTCH1, and XPA located in this region in the development of HNSCC. Methods The alterations (deletion, promoter methylation, mutation, expression) of these genes were analyzed in 65 dysplastic head and neck lesions and 84 primary HNSCC samples. Clinicopathologic correlations were made with alterations of the genes. Results Overall alterations (deletion, promoter methylation) of FANCC and PTCH1 were high in mild dysplasia and comparable in subsequent stages of tumor progression. However, PHF2 alteration was low in mild dysplasia, but increased in moderate and severe dysplasias. Alterations (deletion, promoter methylation) of FANCC and PTCH1 showed association with each other. Two novel mutations in GLI binding sites of PTCH1 promoter and a novel microsatellite marker hmPTCH1 with four alleles at immediate upstream of the gene were identified. In a case-control study, the (CGG)7 allele of hmPTCH1 was found to be susceptible for HNSCC development. Concordance was seen in the expression (RNA, protein) of these genes with their molecular alterations. Conclusions Alterations of FANCC and PTCH1 could be used as molecular marker for early diagnosis and prognosis of HNSCC.