Lip cancer and pre-cancerous lesions harbor TP53 mutations, exhibit allelic loss at 9p, 9q, and 17p, but no BRAFV600E mutations
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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.
KeywordsActinic cheilitis LOH p53 Potentially malignant oral lesions Lip squamous cell carcinoma Head and neck cancer
This study was supported in part by the following Brazilian funding agencies: Coordination for the Improvement of Higher Education Personnel (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and National Council for Scientific and Technological Development (CNPq), Brazil. R.S. Gomez, C.C. Gomes, De-Paula A.M.B., and R.P. Souza are research fellows at CNPq. The authors acknowledge the Centro de Aquisição e Processamento de Imagens (CAPI- ICB/UFMG) for the LMD technical support.
Conflicts of interest
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