Clinical Oral Investigations

, Volume 19, Issue 9, pp 2273–2283

Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma

  • Iman Salahshourifar
  • Vui King Vincent-Chong
  • Hong-Yun Chang
  • Hooi Leng Ser
  • Anand Ramanathan
  • Thomas George Kallarakkal
  • Zainal Ariff Abdul Rahman
  • Siti Mazlipah Ismail
  • Narayanan Prepageran
  • Wan Mahadzir Wan Mustafa
  • Mannil Thomas Abraham
  • Keng Kiong Tay
  • Rosnah Binti Zain
Original Article

Abstract

Objectives

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.

Materials and 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).

Conclusion

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.

Clinical relevance

Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.

Keywords

Oral squamous cell carcinoma CRNN gene Genetic instability 1q23.1. LOH/MSI 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Iman Salahshourifar
    • 1
  • Vui King Vincent-Chong
    • 1
  • Hong-Yun Chang
    • 1
  • Hooi Leng Ser
    • 1
  • Anand Ramanathan
    • 1
    • 2
  • Thomas George Kallarakkal
    • 1
    • 2
  • Zainal Ariff Abdul Rahman
    • 1
    • 2
  • Siti Mazlipah Ismail
    • 1
    • 2
  • Narayanan Prepageran
    • 1
    • 3
  • Wan Mahadzir Wan Mustafa
    • 4
  • Mannil Thomas Abraham
    • 5
  • Keng Kiong Tay
    • 6
  • Rosnah Binti Zain
    • 1
    • 2
  1. 1.Oral Cancer Research and Coordinating Centre, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia
  2. 2.Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia
  3. 3.Department of Otorhinolaringology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  4. 4.Department of Oral and Maxillofacial Surgery, Hospital Kuala LumpurMinistry of Health MalaysiaKuala LumpurMalaysia
  5. 5.Department of Oral and Maxillofacial Surgery, Hospital Tengku Ampuan RahimahMinistry of Health MalaysiaKlangMalaysia
  6. 6.Department of Oral Surgery, Hospital Umum SarawakMinistry of Health MalaysiaKuchingMalaysia

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