Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

Uchida, Kenichiro; Oga, Atsunori; Nakao, Motonao; Mano, Takamitsu; Mihara, Mariko; Kawauchi, Shigeto; Furuya, Tomoko; Ueyama, Yoshiya; Sasaki, Kohsuke

doi:10.3892/or.2011.1327

Cited by 15 publications

(17 citation statements)

References 34 publications

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“…We hypothesize that these alterations are potential predictive biomarkers of lymph node metastasis. According to previous studies, the amplification of 8q24.21 and the deletion of 3p26.3 are associated with metastasis, invasion, and therapy resistance [20], [21].…”

Section: Resultsmentioning

confidence: 90%

Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

Bhosale

Cristea

Ambatipudi

et al. 2017

Translational Oncology

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We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1 (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis.

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Section: Resultsmentioning

confidence: 90%

Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

Bhosale

Cristea

Ambatipudi

et al. 2017

Translational Oncology

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“…Copy number analysis on LRP12, TPM2, EGFR, FSCN1, CCND1, CLPTM1L, CHL1 and CSMD1 genes were carried out using qPCR. The rationale of choosing these CNA associated genes was basically due to LRP12, TPM2, EGFR, CCND1 being matched with ICGC and TCGA databases whereas FSCN1, CLPTM1L, CHL1 and CSMD1 had been found to be associated with oral cancer [12, 31–33]. This study attempted to elucidate whether these genes were the driver genes in the CNA regions which is 7p, 5p, 3p and 8p.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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BackgroundCancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy.ObjectivesThe current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes.Materials and methodsUsing array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software.ResultsMultiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC.ConclusionAmplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways.

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“…The BAC clones in this platform were established by Macrogen, Inc. The experiments were performed as previously described (21)(22)(23).…”

Section: Array-based Comparative Genomic Hybridization (A-cgh)mentioning

confidence: 99%

Loss of 6q or 8p23 is associated with the total number of DNA copy number aberrations in adenoid cystic carcinoma

et al. 2011

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Abstract. We analyzed 10 adenoid cystic carcinomas (ACCs) of the salivary glands by array-based comparative genomic hybridization (a-CGH) using DNA chips spotted with 4,030 bacterial artificial chromosome clones. After the data smoothing procedure was applied, a total of 88 DNA copy number aberrations (DCNAs) were detected. The frequent (≥30%) DCNAs were loss of 6q23-27 and 8p23, and gains of 6p, 6q23, 8p23 and 22q13. High-level gains were detected on 12q15, including MDM2 in two cases. These two cases showed an immunohistochemically high-level (>50%) expression of MDM2 and a low-level expression of p53 (<20%). Furthermore, the total number of DCNAs was significantly greater in ACCs with loss of 6q compared to other ACCs, and in ACCs without the loss of 8p23 compared to other ACCs, respectively. Although limitations exist, a-CGH detected several candidate chromosomal imbalances associated with accumulation of DCNAs in ACCs.

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Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

Cited by 15 publications

References 34 publications

Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

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

Loss of 6q or 8p23 is associated with the total number of DNA copy number aberrations in adenoid cystic carcinoma

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