title: Association of FANCC and PTCH1 with the development of early dysplastic lesions of the head and neck.
abstract: 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.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Amlan
authors.initials: A
authors.lastname: Ghosh
authors.forename: Susmita
authors.initials: S
authors.lastname: Ghosh
authors.forename: Guru Prasad
authors.initials: GP
authors.lastname: Maiti
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Nupur
authors.initials: N
authors.lastname: Mukherjee
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chakraborty
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.forename: C K
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D016001:Confidence Intervals; D004279:DNA, Viral / Q000302:isolation & purification; D052218:Fanconi Anemia Complementation Group C Protein / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D018398:Homeodomain Proteins / Q000235:genetics; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016017:Odds Ratio; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000235:genetics*; D017384:Sequence Deletion; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D004279:DNA, Viral; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D018398:Homeodomain Proteins; C117905:PHF2 protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein