TY - JOUR T1 - Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis. JF - Clin Cancer Res Y1 - 2011 A1 - Bhattacharya, Aditi A1 - Roy, Ritu A1 - A Snijders A1 - Hamilton, Gregory A1 - Paquette, Jesse A1 - Tokuyasu, Taku A1 - Bengtsson, Henrik A1 - Jordan, Richard C K A1 - Olshen, Adam B A1 - Pinkel, Daniel A1 - Schmidt, Brian L A1 - Albertson, Donna G KW - Carcinoma, Squamous Cell KW - Cohort Studies KW - Comparative Genomic Hybridization KW - Disease Progression KW - DNA Copy Number Variations KW - Female KW - Genomic Instability KW - Head and Neck Neoplasms KW - Humans KW - Lymphatic Metastasis KW - Male KW - Middle Aged KW - Mouth Neoplasms KW - Precancerous Conditions KW - Risk AB -

PURPOSE: 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.

EXPERIMENTAL DESIGN: 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.

VL - 17 IS - 22 ER -