Abstract
Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1–q22.2 and losses of 17p13.3 and 11q23–q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers.
Highlights
Oral squamous cell carcinoma (OSCC) is a major cause of morbidity and mortality worldwide, accounting for more than 275,000 new cases and over 120,000 deaths every year [1]
Gains mapped on chromosomal arms 3q, 6q, 8q, 9p, 9q, 11p, 11q, 14q, 17q, and 20q and losses mapped on 3p, 4q, 9p, and 18q have suggested putative oncogenes and tumor suppressor genes associated with oral cancer [7,8,9,10,11,12,13,14,15]
The present study aims at delineating genome-wide copy number alterations (CNAs) in oral cancer and to understand whether these genetic alterations are associated with clinical characteristics and prognosis
Summary
Oral squamous cell carcinoma (OSCC) is a major cause of morbidity and mortality worldwide, accounting for more than 275,000 new cases and over 120,000 deaths every year [1]. There have been improvements in the therapeutic modalities, OSCC-associated morbidity and mortality remain high and have not changed in over three decades [2]. This lack of improvement in survival indicates that tumor size, lymph node involvement and stage, which are considered as markers of disease aggressiveness, do not sufficiently account for the observed variability in clinical outcomes [3]. Gains mapped on chromosomal arms 3q, 6q, 8q, 9p, 9q, 11p, 11q, 14q, 17q, and 20q and losses mapped on 3p, 4q, 9p, and 18q have suggested putative oncogenes and tumor suppressor genes associated with oral cancer [7,8,9,10,11,12,13,14,15].
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