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, DOI


Download (767kB)


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
Additional Information: ISI Document Delivery No.: 092WJ Times Cited: 0 Cited Reference Count: 69 Cited References: Albertson DG, 2006, TRENDS GENET, V22, P447, DOI 10.1016/j.tig.2006.06.007 Albertson DG, 2003, NAT GENET, V34, P369, DOI 10.1038/ng1215 Ambatipudi S, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0017250 Baldwin C, 2005, CANCER RES, V65, P7561, DOI 10.1158/0008-5472.CAN-05-1513 Bhatnagar R, 2012, ORAL ONCOL, V48, P831, DOI 10.1016/j.oraloncology.2012.03.007 Birnbaum D, 2003, LANCET ONCOL, V4, P639, DOI 10.1016/S1470-2045(03)01225-7 Bronstad I, 2011, BMC MED GENET, V12, DOI 10.1186/1471-2350-12-111 Bueno R, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0010612 Camps J, 2008, CANCER RES, V68, P1284, DOI 10.1158/0008-5472.CAN-07-2864 Carter SL, 2006, NAT GENET, V38, P1043, DOI 10.1038/ng1861 Choi P, 2008, ARCH OTOLARYNGOL, V134, P539, DOI 10.1001/archotol.134.5.539 Chu SH, 2012, MOL BIOL RE IN PRESS Cooke SL, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-288 Dittmer Jurgen, 2003, Mol Cancer, V2, P29, DOI 10.1186/1476-4598-2-29 Duffy Michael J, 2011, Clin Proteomics, V8, P9, DOI 10.1186/1559-0275-8-9 Flossbach L, 2012, INT J CANC IN PRESS Freier K, 2010, GENE CHROMOSOME CANC, V49, P9, DOI 10.1002/gcc.20714 Fry JL, 2010, CANCER RES, V70, P8187, DOI 10.1158/0008-5472.CAN-09-4231 Garnis C, 2004, ORAL ONCOL, V40, P511, DOI 10.1016/j.oraloncology.2003.10.006 Gelsi-Boyer Veronique, 2005, Mol Cancer Res, V3, P655, DOI 10.1158/1541-7786.MCR-05-0128 Hamada T, 2012, CANCER IN PRESS Hastings PJ, 2009, NAT REV GENET, V10, P551, DOI 10.1038/nrg2593 Hirotsune S, 2003, NATURE, V423, P91, DOI 10.1038/nature01535 Hossini AM, 2008, BIOCHEM PHARMACOL, V76, P1612, DOI 10.1016/j.bcp.2008.08.013 Jarvinen AK, 2008, GENE CHROMOSOME CANC, V47, P500, DOI 10.1002/gcc.20551 Johnson NW, 2003, ORAL CANC, P3 Jones FS, 2000, DEV DYNAM, V218, P235, DOI 10.1002/(SICI)1097-0177(200006)218:2<235::AID-DVDY2>3.0.CO;2-G Kohn KW, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035716 Kornberg LJ, 1998, HEAD NECK-J SCI SPEC, V20, P745, DOI 10.1002/(SICI)1097-0347(199812)20:8<745::AID-HED14>3.0.CO;2-Z Kufe DW, 2009, NAT REV CANCER, V9, P874, DOI 10.1038/nrc2761 Li Jian, 2010, BMC Res Notes, V3, P321, DOI 10.1186/1756-0500-3-321 Liu CJ, 2006, MOL CARCINOGEN, V45, P721, DOI 10.1002/mc.20213 Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262 Lohavanichbutr P, 2009, ARCH OTOLARYNGOL, V135, P180, DOI 10.1001/archoto.2008.540 Lopez-Nieva P, 2012, CARCINOGENESIS, V33, P452, DOI 10.1093/carcin/bgr271 Martin-Ezquerra G, 2011, HISTOL HISTOPATHOL, V26, P71 Miller DA, 2008, FILM QUART, V62, P12, DOI 10.1525/FQ.2008.62.2.12, 10.1525/FQ.2008.62.1.12 Miller DT, 2010, AM J HUM GENET, V86, P749, DOI 10.1016/j.ajhg.2010.04.006 Mochizuki S, 2007, CANCER SCI, V98, P621, DOI 10.1111/j.1349-7006.2007.00434.x Nagaraj NS, 2007, TOXICOL LETT, V170, P134, DOI 10.1016/j.toxlet.2007.02.014 Naylor TL, 2005, BREAST CANCER RES, V7, pR1186, DOI 10.1186/bcr1356 Parkin DM, 2005, CA-CANCER J CLIN, V55, P74 Peng CH, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0023452 Przybytkowski E, 2011, BMC MED GENOMICS, V4, P1 Ramsay AG, 2007, CANCER RES, V67, P5275, DOI 10.1158/0008-5472.CAN-07-0318 Reshmi SC, 2005, J DENT RES, V84, P107 Romer MU, 2012, MOL ONCOL IN PRESS Rotger M, 2007, PHARMACOGENET GENOM, V17, P885, DOI 10.1097/FPC.0b013e3282ef5cd1 Roymans D, 2001, EUR J BIOCHEM, V268, P487, DOI 10.1046/j.1432-1327.2001.01936.x Sim L, 2010, J BIOL CHEM, V285, P17763, DOI 10.1074/jbc.M109.078980 Sircoulomb F, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-539 Snijders AM, 2005, ONCOGENE, V24, P4232, DOI 10.1038/sj.onc.1208601 Sparano A, 2006, LARYNGOSCOPE, V116, P735, DOI 10.1097/01.mlg.0000205141.54471.7f Sriram KB, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0030398 Stephens PJ, 2011, CELL, V144, P27, DOI 10.1016/j.cell.2010.11.055 Tan DSP, 2007, LAB INVEST, V87, P737, DOI 10.1038/labinvest.3700593 Thean LF, 2010, GENE CHROMOSOME CANC, V49, P99, DOI 10.1002/gcc.20724 Trebinska A, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-76 Tsui IFL, 2010, HEAD NECK-J SCI SPEC, V32, P1143, DOI 10.1002/hed.21311 Tsui IFL, 2009, INT J CANCER, V125, P2219, DOI 10.1002/ijc.24611 Vander Heiden MG, 2011, NAT REV DRUG DISCOV, V10, P671, DOI 10.1038/nrd3504 Venkatraman ES, 2007, BIOINFORMATICS, V23, P657, DOI 10.1093/bioinformatics/btl646 Viet CT, 2010, HEAD NECK-J SCI SPEC, V32, P1246, DOI 10.1002/hed.21358 Vincent-Chong VK, 2011, ORAL DIS, V18, P469 Visani G, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0027560 Xu C, 2010, MOL CANCER, V9, DOI 10.1186/1476-4598-9-143 Yang SH, 2007, INT J MOL MED, V20, P225 Zain RB, 2012, CELL TISSUE IN PRESS Zhang F, 2009, NAT GENET, V41, P849, DOI 10.1038/ng.399 Vincent-Chong, Vui King Anwar, Arif Karen-Ng, Lee Peng Cheong, Sok Ching Yang, Yi-Hsin Pradeep, Padmaja Jayaprasad Rahman, Zainal Ariff Abdul Ismail, Siti Mazlipah Zaini, Zuraiza Mohamad Prepageran, Narayanan Kallarakkal, Thomas George Ramanathan, Anand Mohayadi, Nur Aaina Binti Mohd Rosli, Nurul 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

Actions (login required)

View Item View Item