Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9
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 affect...
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0054705 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0054705</identifier><identifier>PMID: 23405089</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>ADAM Proteins - biosynthesis ; ADAM Proteins - genetics ; alpha-Glucosidases - biosynthesis ; alpha-Glucosidases - genetics ; Amplification ; Amylases ; Analysis ; Annotations ; Bioindicators ; Biology ; Biomarkers ; Cancer ; Cancer genetics ; Carcinogenesis ; Carcinogens ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - genetics ; Care and treatment ; Cell adhesion & migration ; Chromosome 11 ; Chromosome 8 ; Chromosome Aberrations ; Cloning ; Copy number ; Cytogenetics ; Dentistry ; Diagnosis ; DNA Copy Number Variations ; DNA polymerases ; Gene amplification ; Gene expression ; Genes ; Genetic aspects ; Genome-Wide Association Study - methods ; Genomes ; Genomic instability ; Genomics ; Glucoamylase ; Glucosidase ; Health aspects ; Humans ; Hybridization ; Maxillofacial surgery ; Medical diagnosis ; Medical prognosis ; Medical research ; Medicine ; Membrane Proteins - biosynthesis ; Membrane Proteins - genetics ; Metalloproteinase ; Morbidity ; Mortality ; Mouth Mucosa - enzymology ; Mouth Mucosa - pathology ; Mouth Neoplasms - enzymology ; Mouth Neoplasms - genetics ; Oral cancer ; Oral carcinoma ; Oral hygiene ; Oral squamous cell carcinoma ; Overexpression ; Pathology ; Polymerase chain reaction ; RNA ; RNA, Messenger - genetics ; RNA-directed DNA polymerase ; SHPS-1 protein ; Squamous cell carcinoma ; Stability ; Studies ; Surgery ; Tumors ; α-Glucosidase</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e54705</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Vincent-Chong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Vincent-Chong et al 2013 Vincent-Chong et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f2d7a522f76b19e4eed65e6fac666af122312b230803bc2d38d6487db76209833</citedby><cites>FETCH-LOGICAL-c692t-f2d7a522f76b19e4eed65e6fac666af122312b230803bc2d38d6487db76209833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566089/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566089/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23405089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vincent-Chong, Vui King</creatorcontrib><creatorcontrib>Anwar, Arif</creatorcontrib><creatorcontrib>Karen-Ng, Lee Peng</creatorcontrib><creatorcontrib>Cheong, Sok Ching</creatorcontrib><creatorcontrib>Yang, Yi-Hsin</creatorcontrib><creatorcontrib>Pradeep, Padmaja Jayaprasad</creatorcontrib><creatorcontrib>Rahman, Zainal Ariff Abdul</creatorcontrib><creatorcontrib>Ismail, Siti Mazlipah</creatorcontrib><creatorcontrib>Zaini, Zuraiza Mohamad</creatorcontrib><creatorcontrib>Prepageran, Narayanan</creatorcontrib><creatorcontrib>Kallarakkal, Thomas George</creatorcontrib><creatorcontrib>Ramanathan, Anand</creatorcontrib><creatorcontrib>Mohayadi, Nur Aaina Binti Mohd</creatorcontrib><creatorcontrib>Rosli, Nurul Shielawati Binti Mohamed</creatorcontrib><creatorcontrib>Mustafa, Wan Mahadzir Wan</creatorcontrib><creatorcontrib>Abraham, Mannil Thomas</creatorcontrib><creatorcontrib>Tay, Keng Kiong</creatorcontrib><creatorcontrib>Zain, Rosnah Binti</creatorcontrib><title>Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>ADAM Proteins - biosynthesis</subject><subject>ADAM Proteins - genetics</subject><subject>alpha-Glucosidases - biosynthesis</subject><subject>alpha-Glucosidases - genetics</subject><subject>Amplification</subject><subject>Amylases</subject><subject>Analysis</subject><subject>Annotations</subject><subject>Bioindicators</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Carcinoma, Squamous Cell - enzymology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Care and treatment</subject><subject>Cell adhesion & migration</subject><subject>Chromosome 11</subject><subject>Chromosome 8</subject><subject>Chromosome Aberrations</subject><subject>Cloning</subject><subject>Copy number</subject><subject>Cytogenetics</subject><subject>Dentistry</subject><subject>Diagnosis</subject><subject>DNA Copy Number Variations</subject><subject>DNA polymerases</subject><subject>Gene amplification</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genomic instability</subject><subject>Genomics</subject><subject>Glucoamylase</subject><subject>Glucosidase</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Maxillofacial surgery</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - genetics</subject><subject>Metalloproteinase</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Mouth Mucosa - enzymology</subject><subject>Mouth Mucosa - pathology</subject><subject>Mouth Neoplasms - enzymology</subject><subject>Mouth Neoplasms - genetics</subject><subject>Oral cancer</subject><subject>Oral carcinoma</subject><subject>Oral hygiene</subject><subject>Oral squamous cell carcinoma</subject><subject>Overexpression</subject><subject>Pathology</subject><subject>Polymerase chain reaction</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA-directed DNA polymerase</subject><subject>SHPS-1 protein</subject><subject>Squamous cell carcinoma</subject><subject>Stability</subject><subject>Studies</subject><subject>Surgery</subject><subject>Tumors</subject><subject>α-Glucosidase</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAYhc3YWLtu_2BsgsFgF0llSZatm0HotizQUNjXrZCl14mCbaWSnbXsz09p3BLDBsUXNq-ecyQdnyR5neJpSvP0fON636p6unUtTDHOWI6zJ8lpKiiZcILp06Pvk-RFCJsI0YLz58kJoQxnuBCnyZ85tK4B9NsaQCr63QYbkKuQXnvXuOAaVSNVd-BVZ10bkG2R83EWrnvVuD4gDXWNtPLaRiMVkIcdqBoMcjvwCG62HkKI0r3pcj5bxl0Mmn2aLcXL5Fml6gCvhvdZ8vPL5x8XXyeXV_PFxexyorkg3aQiJlcZIVXOy1QAAzA8A14pzTlXVUoITUlJKC4wLTUxtDCcFbkp83h1UVB6lrw9-G5rF-SQW5ApjZI8LwSLxOJAGKc2cutto_ytdMrKu4HzK6l8Z3UNsswyXnKgTAjCqCFCGJ3jsqhYqRQQiF4fh936sgGjoe1iXiPT8Upr13LldpJmnMd_Eg3eDQbeXfcQuv8ceaBWMWxp28pFM93YoOWM5QVLacFIpKb_oOJjoLE6NqeycT4SfBgJItPBTbdSfQhy8f3b49mrX2P2_RG7jg3p1sHV_V2pxiA7gNq7EDxUD8mlWO6Lf5-G3BdfDsWPsjfHqT-I7ptO_wIHzf5_</recordid><startdate>20130206</startdate><enddate>20130206</enddate><creator>Vincent-Chong, 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wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f2d7a522f76b19e4eed65e6fac666af122312b230803bc2d38d6487db76209833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>ADAM Proteins - biosynthesis</topic><topic>ADAM Proteins - genetics</topic><topic>alpha-Glucosidases - biosynthesis</topic><topic>alpha-Glucosidases - genetics</topic><topic>Amplification</topic><topic>Amylases</topic><topic>Analysis</topic><topic>Annotations</topic><topic>Bioindicators</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cancer genetics</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Carcinoma, Squamous Cell - enzymology</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Care and treatment</topic><topic>Cell adhesion & migration</topic><topic>Chromosome 11</topic><topic>Chromosome 8</topic><topic>Chromosome Aberrations</topic><topic>Cloning</topic><topic>Copy number</topic><topic>Cytogenetics</topic><topic>Dentistry</topic><topic>Diagnosis</topic><topic>DNA Copy Number Variations</topic><topic>DNA polymerases</topic><topic>Gene amplification</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genomes</topic><topic>Genomic instability</topic><topic>Genomics</topic><topic>Glucoamylase</topic><topic>Glucosidase</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Maxillofacial surgery</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - genetics</topic><topic>Metalloproteinase</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Mouth Mucosa - enzymology</topic><topic>Mouth Mucosa - pathology</topic><topic>Mouth Neoplasms - enzymology</topic><topic>Mouth Neoplasms - genetics</topic><topic>Oral cancer</topic><topic>Oral carcinoma</topic><topic>Oral hygiene</topic><topic>Oral squamous cell carcinoma</topic><topic>Overexpression</topic><topic>Pathology</topic><topic>Polymerase chain reaction</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA-directed DNA polymerase</topic><topic>SHPS-1 protein</topic><topic>Squamous cell carcinoma</topic><topic>Stability</topic><topic>Studies</topic><topic>Surgery</topic><topic>Tumors</topic><topic>α-Glucosidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vincent-Chong, Vui King</creatorcontrib><creatorcontrib>Anwar, Arif</creatorcontrib><creatorcontrib>Karen-Ng, Lee Peng</creatorcontrib><creatorcontrib>Cheong, Sok Ching</creatorcontrib><creatorcontrib>Yang, Yi-Hsin</creatorcontrib><creatorcontrib>Pradeep, Padmaja Jayaprasad</creatorcontrib><creatorcontrib>Rahman, Zainal Ariff Abdul</creatorcontrib><creatorcontrib>Ismail, Siti Mazlipah</creatorcontrib><creatorcontrib>Zaini, Zuraiza Mohamad</creatorcontrib><creatorcontrib>Prepageran, Narayanan</creatorcontrib><creatorcontrib>Kallarakkal, Thomas George</creatorcontrib><creatorcontrib>Ramanathan, Anand</creatorcontrib><creatorcontrib>Mohayadi, Nur Aaina Binti Mohd</creatorcontrib><creatorcontrib>Rosli, Nurul Shielawati Binti Mohamed</creatorcontrib><creatorcontrib>Mustafa, Wan Mahadzir Wan</creatorcontrib><creatorcontrib>Abraham, Mannil Thomas</creatorcontrib><creatorcontrib>Tay, Keng Kiong</creatorcontrib><creatorcontrib>Zain, Rosnah Binti</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 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Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vincent-Chong, Vui King</au><au>Anwar, Arif</au><au>Karen-Ng, Lee Peng</au><au>Cheong, Sok Ching</au><au>Yang, Yi-Hsin</au><au>Pradeep, Padmaja Jayaprasad</au><au>Rahman, Zainal Ariff Abdul</au><au>Ismail, Siti Mazlipah</au><au>Zaini, Zuraiza Mohamad</au><au>Prepageran, Narayanan</au><au>Kallarakkal, Thomas George</au><au>Ramanathan, Anand</au><au>Mohayadi, Nur Aaina Binti Mohd</au><au>Rosli, Nurul Shielawati Binti Mohamed</au><au>Mustafa, Wan Mahadzir Wan</au><au>Abraham, Mannil Thomas</au><au>Tay, Keng Kiong</au><au>Zain, Rosnah Binti</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-02-06</date><risdate>2013</risdate><volume>8</volume><issue>2</issue><spage>e54705</spage><pages>e54705-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23405089</pmid><doi>10.1371/journal.pone.0054705</doi><tpages>e54705</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-02, Vol.8 (2), p.e54705 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330877894 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | ADAM Proteins - biosynthesis ADAM Proteins - genetics alpha-Glucosidases - biosynthesis alpha-Glucosidases - genetics Amplification Amylases Analysis Annotations Bioindicators Biology Biomarkers Cancer Cancer genetics Carcinogenesis Carcinogens Carcinoma, Squamous Cell - enzymology Carcinoma, Squamous Cell - genetics Care and treatment Cell adhesion & migration Chromosome 11 Chromosome 8 Chromosome Aberrations Cloning Copy number Cytogenetics Dentistry Diagnosis DNA Copy Number Variations DNA polymerases Gene amplification Gene expression Genes Genetic aspects Genome-Wide Association Study - methods Genomes Genomic instability Genomics Glucoamylase Glucosidase Health aspects Humans Hybridization Maxillofacial surgery Medical diagnosis Medical prognosis Medical research Medicine Membrane Proteins - biosynthesis Membrane Proteins - genetics Metalloproteinase Morbidity Mortality Mouth Mucosa - enzymology Mouth Mucosa - pathology Mouth Neoplasms - enzymology Mouth Neoplasms - genetics Oral cancer Oral carcinoma Oral hygiene Oral squamous cell carcinoma Overexpression Pathology Polymerase chain reaction RNA RNA, Messenger - genetics RNA-directed DNA polymerase SHPS-1 protein Squamous cell carcinoma Stability Studies Surgery Tumors α-Glucosidase |
| title | Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9 |
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