title: Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma.
abstract: OBJECTIVE
  This study includes the direct sequencing of cornulin (CRNN) gene to elucidate the possible mechanism of CRNN downregulation and explore the genetic imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples.
  
  
  METHODS
  In mutation screening of CRNN gene, gDNA from OSCC tissues were extracted, amplified, and followed by direct sequencing. OSCC samples were also subjected to fragment analysis on CRNN gene to investigate its microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was performed to validate CRNN downregulation in OSCC samples.
  
  
  RESULTS
  No pathogenic mutation was found in CRNN gene, while high frequency of allelic imbalances was found at 1q21.3 region. MSI was found more frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI which reflects higher probability of inactivation of DNA mismatch repair genes. MSI showed significant association with no betel quid chewing (p = 0.003) and tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p = 0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was associated with poor prognosis (p = 0.044).
  
  
  CONCLUSIONS
  This study showed a significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that downregulation of CRNN gene could be considered as a prognostic marker of OSCC.
  
  
  CONCLUSIONS
  Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
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: 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.
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hooi Leng
authors.initials: HL
authors.lastname: Ser
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Anand
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.|Department of Oro-Maxillofacial Surgical and Medical 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 Oro-Maxillofacial Surgical and Medical 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 Oro-Maxillofacial Surgical and Medical 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 Otorhinolaringology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Prepageran
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital Kuala Lumpur, Ministry of Health Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Wan Mahadzir Wan
authors.initials: WM
authors.lastname: Mustafa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital Tengku Ampuan Rahimah, Ministry of Health Malaysia, Klang, Malaysia.
authors.forename: Mannil Thomas
authors.initials: MT
authors.lastname: Abraham
authors.affiliation: Department of Oral Surgery, Hospital Umum Sarawak, Ministry of Health Malaysia, 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. rosnahbz12@yahoo.com.|Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. rosnahbz12@yahoo.com.
authors.forename: Rosnah Binti
authors.initials: RB
authors.lastname: Zain
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D015536:Down-Regulation; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008296:Malaysia; D008565:Membrane Proteins / Q000235:genetics*; D053842:Microsatellite Instability; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: C418764:CRNN protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins
keywords: 1q23.1. LOH/MSI; CRNN gene; Genetic instability; Oral squamous cell carcinoma
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