Genome-wide disease association study in chewing tobacco associated oral cancers

Bhatnagar, Renu; Dabholkar, Jyoti; Saranath, Dhananjaya

doi:10.1016/j.oraloncology.2012.03.007

Cited by 28 publications

(27 citation statements)

References 29 publications

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“…This suggested the possibility of copy number polymorphism of this region in OSCC genome. Similarly, amplification of chromosome 2p22.3 was identified in genome wide association study with oral cancer patients that were highly exposed to chewing tobacco [58]. This implies chewing tobacco could lead to CNA amplification in this region and lead to OSCC.…”

Section: Discussionmentioning

confidence: 84%

Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 84%

Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9

et al. 2013

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“…identified upregulation of CNTNAP2 mRNA levels as a distinctive characteristic of OSCC in comparison with normal mucosa [32]. In a genome-wide association study for oral cancers, CNTNAP2 was found to be associated with cell migration [42]. The CNTNAP2 gene also functions as a cell adhesion molecule and has been found to be either methylated or deleted in several different cancer types, e.g.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

et al. 2014

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BackgroundSquamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness.MethodsTo extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models.ResultsWe found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively.ConclusionsTaken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.

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“…In India, oral cancer is primarily attributed to the highly prevalent tobacco chewing habit, with early initiation of the tobacco habit at 9-12 years [4]. Besides, the genomic constitution of an individual as indicated by specific genetic variants represented as single nucleotide polymorphisms, and the epigenetic modifications, provide a conducive genomic milieu increasing susceptibility and high risk to oral cancer [5][6][7][8][9]. Epigenetic modifications include hypermethylation in the promoter region of genes, post-translational histone modifications and post-transcriptional regulation by microRNAs.…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of epigenetic regulation in oral cancer

D’Souza

Saranath

2015

Oral Oncology

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Genome-wide disease association study in chewing tobacco associated oral cancers

Cited by 28 publications

References 29 publications

Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9

Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

Clinical implications of epigenetic regulation in oral cancer

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