Genomic aberrations in normal appearing mucosa fields distal from oral potentially malignant lesions

W. Giaretti, M. Maffei, M. Pentenero, P. Scaruffi, A. Donadini, E. Di Nallo, D. Malacarne, R. Marino, U. Familiari, S. Coco, G. P. Tonini, P. Castagnola, S. Gandolfo

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Objectives Oral fields of visually normal and nondysplastic mucosa (ODFs) may represent the precursors of oral potentially malignant lesions (OPMLs). Aim of the study was to provide new evidence for the concept of the "field carcinogenesis" model by comparing the ODF and OPML genomic aberration profiles obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH aberrations were associated with DNA aneuploidy. Methods Nineteen patients with single OPMLs were recruited for the study. In parallel with obtaining samples of OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid nuclei detected by hr DNA-FCM were physically separated, based on DNA content, from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure subpopulations of epithelial nuclei were then submitted to DNA extraction and a-CGH for a genome-wide analysis of DNA copy number aberrations (CNAs). Results The frequencies of DNA aneuploidy (DI≠1) among ODFs and OPMLs were respectively 5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all neardiploid (DI≠1 and DI≤1.4), while for d-OPMLs were highaneuploid (DI>1.4) in 40% of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the chromosomal region 20q13.33-qter was observed in 37% of both ODFs and corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31-q13.33 and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at 9p21.3, gain at 5p13.33-pter and gain of 20q13.31- q13.33 were associated with DNA aneuploidy (p=0.00004; p=0.0005; p=0.01). Conclusions ODFs and OPMLs showed common CNAs in specific chromosomal regions suggesting that they may represent early events of the natural history of oral carcinogenesis according to the field effect cancerization and may contribute to the ODF-OPML transition. In addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31-q13.33 may contribute to DNA aneuploidization.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalCellular Oncology
Issue number1
Publication statusPublished - Feb 2012


  • Comparative genomic hybridization
  • Controlateral distant fields
  • Copy number aberrations
  • DNA aneuploidy
  • Field effect cancerization
  • Flow cytometry
  • Oral potentially malignant lesions

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology
  • Medicine(all)


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