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Published in:

01-12-2015 | Original Article

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

Authors: 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

Published in: Clinical Oral Investigations | Issue 9/2015

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.

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Title: Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma
Authors: 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
Publication date: 01-12-2015
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 9/2015
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-015-1467-7

At a glance: The STEP trials

Springer Medicine

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

Abstract

Objectives

Materials and methods

Results

Conclusion

Clinical relevance

At a glance: The STEP trials

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusion

Clinical relevance

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