title: Unique FISH patterns associated with cancer progression of oral dysplasia.
abstract: Subgroups of patients with oral pre-malignant lesions (OPLs) are at extremely high risk for developing invasive cancer in spite of surgical excision. The objective of this study was to evaluate the utility of specific genes and their associated centromeres as markers to stratify OPLs for their cancer risk. Samples used in this study included 35 oral dysplasia with known outcome and 20 normal oral mucosa. Of the dysplasias, 20 were from an ongoing longitudinal study showing progression. The remaining 15 cases (2 of which progressed) were chosen from the population-based, provincial BC Oral Biopsy Service (OBS). Copy number alterations at EGFR, CEP7, CCND1, and CEP11 were evaluated by fluorescent in situ hybridization (FISH). There was no significant difference in demographics between progressors and non-progressors. Specific FISH profiles at these genes and their corresponding centromeres were associated with progression. High gene gain of CCND1 was associated with an 8-fold elevated risk of progression compared with those with no gain in time-to-progression analysis. Numerical alterations of EGFR and CCND1 and their centromeres might be an effective means for identifying OPLs at risk. Future studies will expand on this analysis and set the stage for application of this approach in routine clinical practice.
authors: Department of Oral Biological and Medical Science, the University of British Columbia, 2199 Wesbrook Mall, Vancouver, BC, Canada. cpoh@interchange.ubc.ca
authors: C F
authors: CF
authors: Poh
authors: Y
authors: Y
authors: Zhu
authors: E
authors: E
authors: Chen
authors: K W
authors: KW
authors: Berean
authors: L
authors: L
authors: Wu
authors: L
authors: L
authors: Zhang
authors: M P
authors: MP
authors: Rosin
mesh_terms: D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002503:Centromere / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D011123:Polyploidy; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors