PMID- 26084614 OWN - NLM STAT- MEDLINE DCOM- 20160329 LR - 20181113 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 36 IP - 11 DP - 2015 Nov TI - Lip cancer and pre-cancerous lesions harbor TP53 mutations, exhibit allelic loss at 9p, 9q, and 17p, but no BRAFV600E mutations. PG - 9059-66 LID - 10.1007/s13277-015-3659-9 [doi] AB - 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. FAU - Correa, Gefter Thiago Batista AU - Correa GT AD - Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Bernardes, Vanessa Fatima AU - Bernardes VF AD - Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil. FAU - de Sousa, Silvia Ferreira AU - de Sousa SF AD - Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Diniz, Marina Goncalves AU - Diniz MG AD - Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Salles, Jose Maria Porcaro AU - Salles JM AD - Department of Surgery, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Souza, Renan Pedra AU - Souza RP AD - Department of General Biology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - De-Paula, Alfredo Mauricio Batista AU - De-Paula AM AD - Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil. FAU - Gomez, Ricardo Santiago AU - Gomez RS AD - Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Gomes, Carolina Cavalieri AU - Gomes CC AD - Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil. carolinacgomes@ufmg.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150618 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.11.1 (BRAF protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) RN - Actinic cheilitis SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Proliferation/*genetics MH - Cheilitis/genetics/pathology MH - Chromosomes, Human, Pair 17/genetics MH - Chromosomes, Human, Pair 9/genetics MH - Exons MH - Female MH - Gene Expression Regulation, Neoplastic MH - Head and Neck Neoplasms/*genetics/pathology MH - Humans MH - Lip Neoplasms/*genetics/pathology MH - Loss of Heterozygosity MH - Male MH - Middle Aged MH - Mutation MH - Proto-Oncogene Proteins B-raf/*genetics MH - Tumor Suppressor Protein p53/biosynthesis/*genetics OTO - NOTNLM OT - Actinic cheilitis OT - Head and neck cancer OT - LOH OT - Lip squamous cell carcinoma OT - Potentially malignant oral lesions OT - p53 EDAT- 2015/06/19 06:00 MHDA- 2016/03/30 06:00 CRDT- 2015/06/19 06:00 PHST- 2015/04/27 00:00 [received] PHST- 2015/06/09 00:00 [accepted] PHST- 2015/06/19 06:00 [entrez] PHST- 2015/06/19 06:00 [pubmed] PHST- 2016/03/30 06:00 [medline] AID - 10.1007/s13277-015-3659-9 [pii] AID - 10.1007/s13277-015-3659-9 [doi] PST - ppublish SO - Tumour Biol. 2015 Nov;36(11):9059-66. doi: 10.1007/s13277-015-3659-9. Epub 2015 Jun 18.