title: Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Vui King
authors.initials: VK
authors.lastname: Vincent-Chong
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Iman
authors.initials: I
authors.lastname: Salahshourifar
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kar Mun
authors.initials: KM
authors.lastname: Woo
authors.affiliation: Sengenics Sdn Bhd, High Impact Research (HIR) Building, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Arif
authors.initials: A
authors.lastname: Anwar
authors.affiliation: Sengenics Sdn Bhd, High Impact Research (HIR) Building, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rozaimi
authors.initials: R
authors.lastname: Razali
authors.affiliation: Sengenics Sdn Bhd, High Impact Research (HIR) Building, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Gudimella
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Zainal Ariff Abdul
authors.initials: ZA
authors.lastname: Rahman
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Siti Mazlipah
authors.initials: SM
authors.lastname: Ismail
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Thomas George
authors.initials: TG
authors.lastname: Kallarakkal
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Anand
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Wan Mahadzir
authors.initials: WM
authors.lastname: Wan Mustafa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital Tengku Ampuan Rahimah, Klang, Selangor Darul Ehsan, Malaysia.
authors.forename: Mannil Thomas
authors.initials: MT
authors.lastname: Abraham
authors.affiliation: Department of Oral Surgery, Hospital Umum Kuching, Kuching, Sarawak, Malaysia.
authors.forename: Keng Kiong
authors.initials: KK
authors.lastname: Tay
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rosnah Binti
authors.initials: RB
authors.lastname: Zain
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction