title: Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis.
abstract: OBJECTIVE
  Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis.
  
  
  METHODS
  The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization. Associations with clinical characteristics were studied and results confirmed in an independent cohort.
  
  
  RESULTS
  The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2, and +20 distinguishes a major subgroup (70%-80% of lesions, termed 3q8pq20 subtype) from the remainder (20%-30% of lesions, non-3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts.
  
  
  CONCLUSIONS
  Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q,-8p, +8q, and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, although increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC.
authors: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94158, USA.
authors: Aditi
authors: A
authors: Bhattacharya
authors: Ritu
authors: R
authors: Roy
authors: Antoine M
authors: AM
authors: Snijders
authors: Gregory
authors: G
authors: Hamilton
authors: Jesse
authors: J
authors: Paquette
authors: Taku
authors: T
authors: Tokuyasu
authors: Henrik
authors: H
authors: Bengtsson
authors: Richard C K
authors: RC
authors: Jordan
authors: Adam B
authors: AB
authors: Olshen
authors: Daniel
authors: D
authors: Pinkel
authors: Brian L
authors: BL
authors: Schmidt
authors: Donna G
authors: DG
authors: Albertson
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D018450:Disease Progression; D005260:Female; D042822:Genomic Instability; D006258:Head and Neck Neoplasms / Q000556:secondary*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D012306:Risk