title: Lip cancer and pre-cancerous lesions harbor TP53 mutations, exhibit allelic loss at 9p, 9q, and 17p, but no BRAFV600E mutations.
abstract: Molecular mechanisms of lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) are unclear. We aimed at assessing loss of heterozygosity (LOH) and TP53 and BRAF V600E mutations in these lesions. Formalin-fixed paraffin-embedded (FFPE) samples of 17 LSCC and 16 AC were included, with additional 5 fresh LSCC genotyped for TP53 mutations. LOH was assessed by six polymorphic markers located at 9p22, 9q22, and 17p13 and correlated with cell proliferation (Ki-67) and P53 immunostaining. Direct sequencing of TP53 exons 2-11 (fresh samples), and exons 5-9 (FFPE samples) was carried out. BRAF V600E mutation was genotyped in eight LSCC. LOH occurred in at least one marker in 15/17 LSCC and in 9/16 AC. The marker exhibiting the highest frequency of allelic loss (FAL) in LSCC was D9S157 (8/12 informative cases) and D9S287 in AC (4/11 informative cases). Cell proliferation was not correlated with LOH or with the FAL and no correlation between P53 IHC and 17p LOH was observed. We found TP53 missense mutations in both lesions and nonsense in LSCC, including CC>TT transition, which is a marker of UV damage. BRAF V600E mutation was not detected. LOH and TP53 mutations detected in LSCC and AC may be associated with tumorigenesis, whereas BRAF V600E mutation does not seem to significantly contribute to LSCC pathogenesis.
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Gefter Thiago Batista
authors.initials: GT
authors.lastname: Correa
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
authors.forename: Vanessa Fátima
authors.initials: VF
authors.lastname: Bernardes
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Silvia Ferreira
authors.initials: SF
authors.lastname: de Sousa
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marina Gonçalves
authors.initials: MG
authors.lastname: Diniz
authors.affiliation: Department of Surgery, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: José Maria Porcaro
authors.initials: JM
authors.lastname: Salles
authors.affiliation: Department of General Biology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Renan Pedra
authors.initials: RP
authors.lastname: Souza
authors.affiliation: Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil.
authors.forename: Alfredo Maurício Batista
authors.initials: AM
authors.lastname: De-Paula
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ricardo Santiago
authors.initials: RS
authors.lastname: Gomez
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil. carolinacgomes@ufmg.br.
authors.forename: Carolina Cavalieri
authors.initials: CC
authors.lastname: Gomes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation / Q000235:genetics*; D002613:Cheilitis / Q000235:genetics / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008048:Lip Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Actinic cheilitis; Head and neck cancer; LOH; Lip squamous cell carcinoma; Potentially malignant oral lesions; p53