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Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance.
- Source :
-
PloS one [PLoS One] 2017 Apr 06; Vol. 12 (4), pp. e0174865. Date of Electronic Publication: 2017 Apr 06 (Print Publication: 2017). - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Carcinoma, Squamous Cell pathology
Comparative Genomic Hybridization
DNA Copy Number Variations
Female
Humans
Male
Middle Aged
Mouth Neoplasms pathology
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
Carcinoma, Squamous Cell genetics
Gene Expression Profiling
Mouth Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28384287
- Full Text :
- https://doi.org/10.1371/journal.pone.0174865