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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 co...

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Autores principales: Vincent-Chong, Vui King, Salahshourifar, Iman, Woo, Kar Mun, Anwar, Arif, Razali, Rozaimi, Gudimella, Ranganath, Rahman, Zainal Ariff Abdul, Ismail, Siti Mazlipah, Kallarakkal, Thomas George, Ramanathan, Anand, Wan Mustafa, Wan Mahadzir, Abraham, Mannil Thomas, Tay, Keng Kiong, Zain, Rosnah Binti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383235/
https://www.ncbi.nlm.nih.gov/pubmed/28384287
http://dx.doi.org/10.1371/journal.pone.0174865
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author Vincent-Chong, Vui King
Salahshourifar, Iman
Woo, Kar Mun
Anwar, Arif
Razali, Rozaimi
Gudimella, Ranganath
Rahman, Zainal Ariff Abdul
Ismail, Siti Mazlipah
Kallarakkal, Thomas George
Ramanathan, Anand
Wan Mustafa, Wan Mahadzir
Abraham, Mannil Thomas
Tay, Keng Kiong
Zain, Rosnah Binti
author_facet Vincent-Chong, Vui King
Salahshourifar, Iman
Woo, Kar Mun
Anwar, Arif
Razali, Rozaimi
Gudimella, Ranganath
Rahman, Zainal Ariff Abdul
Ismail, Siti Mazlipah
Kallarakkal, Thomas George
Ramanathan, Anand
Wan Mustafa, Wan Mahadzir
Abraham, Mannil Thomas
Tay, Keng Kiong
Zain, Rosnah Binti
author_sort Vincent-Chong, Vui King
collection PubMed
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.
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spelling pubmed-53832352017-05-03 Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance Vincent-Chong, Vui King Salahshourifar, Iman Woo, Kar Mun Anwar, Arif Razali, Rozaimi Gudimella, Ranganath Rahman, Zainal Ariff Abdul Ismail, Siti Mazlipah Kallarakkal, Thomas George Ramanathan, Anand Wan Mustafa, Wan Mahadzir Abraham, Mannil Thomas Tay, Keng Kiong Zain, Rosnah Binti PLoS One Research Article 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. Public Library of Science 2017-04-06 /pmc/articles/PMC5383235/ /pubmed/28384287 http://dx.doi.org/10.1371/journal.pone.0174865 Text en © 2017 Vincent-Chong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vincent-Chong, Vui King
Salahshourifar, Iman
Woo, Kar Mun
Anwar, Arif
Razali, Rozaimi
Gudimella, Ranganath
Rahman, Zainal Ariff Abdul
Ismail, Siti Mazlipah
Kallarakkal, Thomas George
Ramanathan, Anand
Wan Mustafa, Wan Mahadzir
Abraham, Mannil Thomas
Tay, Keng Kiong
Zain, Rosnah Binti
Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383235/
https://www.ncbi.nlm.nih.gov/pubmed/28384287
http://dx.doi.org/10.1371/journal.pone.0174865
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