Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance.
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 cop...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5383235?pdf=render |
| _version_ | 1811325295829975040 |
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| author | Vui King Vincent-Chong Iman Salahshourifar Kar Mun Woo Arif Anwar Rozaimi Razali Ranganath Gudimella Zainal Ariff Abdul Rahman Siti Mazlipah Ismail Thomas George Kallarakkal Anand Ramanathan Wan Mahadzir Wan Mustafa Mannil Thomas Abraham Keng Kiong Tay Rosnah Binti Zain |
| author_facet | Vui King Vincent-Chong Iman Salahshourifar Kar Mun Woo Arif Anwar Rozaimi Razali Ranganath Gudimella Zainal Ariff Abdul Rahman Siti Mazlipah Ismail Thomas George Kallarakkal Anand Ramanathan Wan Mahadzir Wan Mustafa Mannil Thomas Abraham Keng Kiong Tay Rosnah Binti Zain |
| author_sort | Vui King Vincent-Chong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T14:30:32Z |
| format | Article |
| id | doaj.art-6b4773035b5348bd948bc3346e40040e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T14:30:32Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6b4773035b5348bd948bc3346e40040e2022-12-22T02:43:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01124e017486510.1371/journal.pone.0174865Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance.Vui King Vincent-ChongIman SalahshourifarKar Mun WooArif AnwarRozaimi RazaliRanganath GudimellaZainal Ariff Abdul RahmanSiti Mazlipah IsmailThomas George KallarakkalAnand RamanathanWan Mahadzir Wan MustafaMannil Thomas AbrahamKeng Kiong TayRosnah Binti ZainBACKGROUND: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.http://europepmc.org/articles/PMC5383235?pdf=render |
| spellingShingle | Vui King Vincent-Chong Iman Salahshourifar Kar Mun Woo Arif Anwar Rozaimi Razali Ranganath Gudimella Zainal Ariff Abdul Rahman Siti Mazlipah Ismail Thomas George Kallarakkal Anand Ramanathan Wan Mahadzir Wan Mustafa Mannil Thomas Abraham Keng Kiong Tay Rosnah Binti Zain Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance. PLoS ONE |
| title | Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance. |
| title_full | Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance. |
| title_fullStr | Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance. |
| title_full_unstemmed | Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance. |
| title_short | Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance. |
| title_sort | genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance |
| url | http://europepmc.org/articles/PMC5383235?pdf=render |
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