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

View Article: PubMed Central - PubMed

ABSTRACT

Background: Cancers 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.

Objectives: The 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 methods: Using 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.

Results: Multiple 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.

Conclusion: Amplification 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.

No MeSH data available.


The ideogram of CNAs identified representing intersection of cytoband CNAs from TCGA and ICGC studies.
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pone.0174865.g002: The ideogram of CNAs identified representing intersection of cytoband CNAs from TCGA and ICGC studies.

Mentions: The regions with a frequency of copy number alterations that was ≥ 8% were reported in this study. In array CGH analysis, 26 amplified and 3 deleted chromosomal regions were found (Table 2 and Fig 1). The number of occurrences, size of the start genome position and end genome position of the CNAs are illustrated in Table 2. In the whole genome wide profiling dataset, amplifications outnumbered deletions. Amplifications in 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletions in 3p and 8p chromosomal regions were recurrent. Amplification in 8q22.3-q23.1 and deletion in 3p21.31 were the most common findings, accounting for 18.7% and 9.3% of all samples, respectively (Table 2). Chromosomal regions 3q, 8q and 11q depicted the largest number of CNAs (Table 2 and Fig 1). There were 11 and 21 CNAs identified from the current study that shared similarities with the TGCA of the oral cancer array CGH OSCC study and the International Cancer Genome Consortium (ICGC) respectively (Fig 2 and S1 Table).


Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance
The ideogram of CNAs identified representing intersection of cytoband CNAs from TCGA and ICGC studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383235&req=5

pone.0174865.g002: The ideogram of CNAs identified representing intersection of cytoband CNAs from TCGA and ICGC studies.
Mentions: The regions with a frequency of copy number alterations that was ≥ 8% were reported in this study. In array CGH analysis, 26 amplified and 3 deleted chromosomal regions were found (Table 2 and Fig 1). The number of occurrences, size of the start genome position and end genome position of the CNAs are illustrated in Table 2. In the whole genome wide profiling dataset, amplifications outnumbered deletions. Amplifications in 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletions in 3p and 8p chromosomal regions were recurrent. Amplification in 8q22.3-q23.1 and deletion in 3p21.31 were the most common findings, accounting for 18.7% and 9.3% of all samples, respectively (Table 2). Chromosomal regions 3q, 8q and 11q depicted the largest number of CNAs (Table 2 and Fig 1). There were 11 and 21 CNAs identified from the current study that shared similarities with the TGCA of the oral cancer array CGH OSCC study and the International Cancer Genome Consortium (ICGC) respectively (Fig 2 and S1 Table).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Cancers 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.

Objectives: The 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 methods: Using 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.

Results: Multiple 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.

Conclusion: Amplification 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.

No MeSH data available.