Two Distinct Routes to Oral Cancer Differing in Genome Instability and Risk for Cervical Node Metastasis

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...

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Bibliographic Details
Published in:	Clinical cancer research 2011-11, Vol.17 (22), p.7024-7034
Main Authors:	BHATTACHARYA, Aditi, ROY, Ritu, SCHMIDT, Brian L, ALBERTSON, Donna G, SNIJDERS, Antoine M, HAMILTON, Gregory, PAQUETTE, Jesse, TOKUYASU, Taku, BENGTSSON, Henrik, JORDAN, Richard C. K, OLSHEN, Adam B, PINKEL, Daniel
Format:	Article
Language:	eng
Subjects:	Antineoplastic agents Biological and medical sciences Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cohort Studies Comparative Genomic Hybridization Disease Progression DNA Copy Number Variations Female Genomic Instability Head and Neck Neoplasms - secondary Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphatic Metastasis Male Medical sciences Middle Aged Mouth Neoplasms - genetics Mouth Neoplasms - pathology Pharmacology. Drug treatments Precancerous Conditions - genetics Precancerous Conditions - pathology Risk
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Summary:	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. 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. 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. 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.
ISSN:	1078-0432 1557-3265