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

TY - JOUR

T1 - 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

AU - Schwarz, Stephan

AU - Bier, Johannes

AU - Driemel, Oliver

AU - Reichert, Torsten E

AU - Hauke, Sven

AU - Hartmann, Arndt

AU - Brockhoff, Gero

N1 - (c) 2007 International Society for Analytical Cytology.

PY - 2008/4

Y1 - 2008/4

N2 - 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.

AB - 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.

KW - Adult

KW - Carcinoma, Squamous Cell

KW - Cell Transformation, Neoplastic

KW - Chromosomes, Human, Pair 3

KW - Chromosomes, Human, Pair 9

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Infant

KW - Keratosis

KW - Leukoplakia

KW - Models, Biological

KW - Mouth Mucosa

KW - Mouth Neoplasms

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/cyto.a.20504

DO - 10.1002/cyto.a.20504

M3 - SCORING: Journal article

C2 - 18163473

VL - 73

SP - 305

EP - 311

JO - CYTOM PART A

JF - CYTOM PART A

SN - 1552-4922

IS - 4

ER -