Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q Alterations as Markers of Poor Clinical Outcome

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.

Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

“…In this current study, we have identified highly frequent copy number alterations in chromosomes 3p, 3q, 8p, 8q and 11q, as described in previous studies that are capable of leading to poor clinical outcome in OSCC [10, 13, 23][10,25,26]. Amplification of 8q22.3-q23.1 was the most frequent event in the current study, and was seen in 18.70% (n = 75) of all OSCCs.…”

“…CNAs have the tendency to disrupt proto-oncogenes or tumour suppressor genes, and are known to be major contributors to poor prognosis of oral cancer [7,9,10]. In this current study, we have identified highly frequent copy number alterations in chromosomes 3p, 3q, 8p, 8q and 11q, as described in previous studies that are capable of leading to poor clinical outcome in OSCC [10, 13, 23][10,25,26].…”

“…Copy number alterations (CNAs) that include amplifications and deletions result in activation of proto-oncogenes and inactivation of tumour suppressor genes, respectively [9]. Several recurrent CNAs have been reported in OSCC by many authors [10–13], but how these CNAs play a role in the pathogenesis of OSCC has not been thus far elucidated. Profiling of CNAs using high-throughput methods provides advanced tools to discover potential biomarkers that could be used for predictive, prognostic and diagnostic approaches [14, 15].…”

Oncogenic Function of SCCRO5/DCUN1D5 Requires Its Neddylation E3 Activity and Nuclear Localization

“…SCCRO5 mRNA overexpression was less common in cancer types with a lower prevalence of 11q22 amplification, including lung adenocarcinomas (2 of 27 [7%]), lung neuroendocrine carcinomas (6 of 54 [11%]), ovarian carcinomas (1 of 40 [3%]), and thyroid carcinomas (5 of 56 [9%]) (Fig. 4A) (26, 27, 30). Moreover, in the cohort of lung SCCs and oral cavity SCCs, SCCRO5 mRNA levels correlated with SCCRO5 protein levels (Fig.…”

Overexpression of ADAM9 in oral squamous cell carcinoma

“…Regarding its involvement in pathologic conditions, ADAM9 overexpression has been identified in a variety of cancer types, including breast cancer (16), renal cancer (17), prostate cancer (18), skin melanoma (19), uterine cervical cancer (20,21), hepatocellular carcinoma (22), non-small cell lung cancer (23), colon cancer (24), gastric cancer (15), esophageal cancer (25) and head and neck squamous cell carcinoma (HNSCC) (26). In the oral cavity, conflicting results of chromosomal aberrations in the ADAM9-containing region have been identified by the array comparative genomic hybridization technique (9,27). Furthermore, no significant difference in ADAM9 mRNA expression has been observed between OSCC and normal tissues, or between oral cancer cell lines and normal oral keratinocytes (9,28).…”