title: Inter- and intra-lesional molecular heterogeneity of oral leukoplakia.
abstract: OBJECTIVE
  Oral leukoplakia (OL) is the most common potentially malignant lesion of the oral cavity, and OL diagnosis is a risk factor for developing subsequent oral squamous cell carcinomas (OSCC). Notably, loss of heterozygosity (LOH) profiles have been validated as risk predictors of malignant transformation of OL. Similar to other solid malignant tumors, OSCC exhibit molecular heterogeneity. However, if and to what extent tumor heterogeneity is present in premalignant lesions of the oral cavity has not been addressed. As LOH analysis is currently being used to stratify OL patients at risk for OSCC development in chemoprevention studies, insight into the issue of molecular heterogeneity of OL is of clinical significance.
  
  
  METHODS
  To address this issue, 11 polymorphic microsatellite markers localizing to chromosomes 3, 9, 11 and 17 were used to detect LOH in 28 samples of 14 OL patients, by capillary electrophoresis analysis. These samples were either clinically recurrent lesions, or two anatomically distinct biopsies from the same lesion, or even two different OL lesions located at distinct intraoral sites.
  
  
  RESULTS
  In all but one of the biopsies pairs, distinct LOH patterns were displayed regardless of histopathological grade. These data provide evidence for inter- and intra-lesional molecular heterogeneity in OL.
  
  
  CONCLUSIONS
  On the basis of these findings, molecular heterogeneity needs to be addressed in subsequent studies targeting specific carcinogenic pathways/genes in chemoprevention of malignant transformation of OL.
authors.affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: carolinacgomes@ufmg.br.
authors.forename: Carolina Cavalieri
authors.initials: CC
authors.lastname: Gomes
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Fonseca-Silva
authors.affiliation: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Clarice Ferreira
authors.initials: CF
authors.lastname: Galvão
authors.affiliation: The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center Tel Hashomer and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.affiliation: Department of Surgery, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Luiz
authors.initials: L
authors.lastname: De Marco
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
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged
keywords: 3p; 9p; LOH, loss of heterozygosity; Oral cancer; Oral dysplasia; Potentially malignant oral disorders