title: Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.
abstract: Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.
authors.affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Castagnola
authors.affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.|Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zoppoli
authors.affiliation: Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gandolfo
authors.affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Monticone
authors.affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Malacarne
authors.affiliation: Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cirmena
authors.affiliation: J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aiello
authors.affiliation: Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffei
authors.affiliation: Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marino
authors.affiliation: IRCCS AOU - San Martino -IST, Genoa, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Giaretti
authors.affiliation: Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Pentenero
mesh_terms: D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D043171:Chromosomal Instability / Q000235:genetics; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D023281:Genomics; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D014059:Tongue / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm