Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9

Vincent-Chong, V.K. and Anwar, A. and Karen-Ng, L.P. and Cheong, S.C. and Yang, Y.H. and Pradeep, P.J. and Rahman, Z.A.A. and Ismail, S.M. and Zaini, Z.M. and Prepageran, N. and Kallarakkal, T.G. and Ramanathan, A. and Mohayadi, N.A.B.M and Rosli, N.S.B.M. and Mustafa, W.M.W. and Abraham, M.T. and Tay, K.K. and Zain, R.B. (2013) Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9. PLoS ONE, 8 (2). ISSN 1932-6203

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Abstract

Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52), 2p22.3(52), 1q21.3-q22(54), 6p21.32(59), 20p13(61), 7q34(52 and 72), 8p11.23-p11.22(80), 8q11.1-q24.4(54), 9q13-q34.3(54), 11q23.3-q25(57); 14q21.3-q31.1(54); 14q31.3-q32.33(57), 20p13-p12.3(54) and 20q11.21-q13.33(52). The most frequently deleted chromosome region was located on 3q26.1 (54). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23-p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that were amplified and resulted in consequent over-expression of the MGAM and ADAM9 genes that may be utilized as biological markers for OSCC.

Item Type: Article
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Shielawati Binti Mohamed Mustafa, Wan Mahadzir Wan Abraham, Mannil Thomas Tay, Keng Kiong Zain, Rosnah Binti University of Malaya High Impact Research Grant J-00000-73561; Ministry of Higher Education High Impact Research Grant H-18001-00-C000008; Ministry of Science, Technology and Innovation E-science grant 02-01-03SF0385 This study was supported by a University of Malaya High Impact Research Grant (J-00000-73561), a Ministry of Higher Education High Impact Research Grant (H-18001-00-C000008) and a Ministry of Science, Technology and Innovation E-science grant (02-01-03SF0385). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Public library science San francisco
Uncontrolled Keywords: Copy number gene-expression cancer array hybridization microarray amplification instability progression migration
Subjects: R Medicine > RK Dentistry
Divisions: Faculty of Dentistry > Dept of Oral Pathology & Oral Medicine & Periodontology
Depositing User: Mr Ahmad Azwan Azman
Date Deposited: 17 Jul 2013 00:14
Last Modified: 05 Jul 2017 01:18
URI: http://eprints.um.edu.my/id/eprint/7742

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