title: Losses of 3p14 and 9p21 as shown by fluorescence in situ hybridization are early events in tumorigenesis of oral squamous cell carcinoma and already occur in simple keratosis.
abstract: Tumorigenesis of oral squamous cell carcinoma (OSCC) has been postulated to represent a multistep process driven by the accumulation of carcinogen-induced genetic changes. Alterations of the 3p14 fragile site containing the fragile histidine triade gene and of the 9p21 tumor suppressor locus containing methylthioadenosine phosphorylase, p16 and p15 characteristically occur in oral leukoplakia, a known precursor of OSCC, and are at present considered to indicate the transition from simple keratosis (hyperplasia) to dysplasia. The aim of the study was to evaluate the occurrence of losses of 3p14 and 9p21 and to evaluate polysomies 3 and 9 in leukoplakias using highly sensitive fluorescence in situ hybridization (FISH) probes. Examining 67 leukoplakias (24 hyperplasias, 33 dysplasias, 10 in situ carcinomas), control tissues of oral mucosa from infants and adults as well as invasive carcinomas and normal epithelia of tumor patients with locus specific FISH probes targeting 3p14 and 9p21, and centromeric probes for chromosomes 3 and 9 we could demonstrate that losses of these sites appeared very early in the tumorigenesis of OSCC and were already present in the great majority of simple keratoses. Polysomy 3 occurring more frequently than polysomy 9 was characteristic of dysplasia and in situ carcinomas and thus seems to follow losses of 3p14 and 9p21 during oral squamous cell carcinogenesis.
authors.affiliation: Department of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany. stephan.schwarz@uk-erlangen.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarz
authors.forename: Johannes
authors.initials: J
authors.lastname: Bier
authors.forename: Oliver
authors.initials: O
authors.lastname: Driemel
authors.forename: Torsten E
authors.initials: TE
authors.lastname: Reichert
authors.forename: Sven
authors.initials: S
authors.lastname: Hauke
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Gero
authors.initials: G
authors.lastname: Brockhoff
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D007642:Keratosis / Q000175:diagnosis* / Q000235:genetics*; D007971:Leukoplakia / Q000235:genetics; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics*