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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-02, Vol.8 (2), p.e54705
Main Authors: 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
Format: Article
Language:English
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0054705