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Delineating the tumour-regulatory roles of EYA4

Chong ZX, Ho WY, Yeap SK

Biochem Pharmacol, 2023 Apr;210:115466.
PMID: 36849065 DOI: 10.1016/j.bcp.2023.115466

Eyes absent homolog 4 (EYA4) is a protein that regulates many vital cellular processes and organogenesis pathways. It possesses phosphatase, hydrolase, and transcriptional activation functions. Mutations in the Eya4 gene can cause sensorineural hearing loss and heart disease. In most non-nervous system cancers such as those of the gastrointestinal tract (GIT), hematological and respiratory systems, EYA4 acts as a putative tumor suppressor. However, in nervous system tumors such as glioma, astrocytoma, and malignant peripheral nerve sheath tumor (MPNST), it plays a putative tumor-promoting role. EYA4 interacts with various signaling proteins of the PI3K/AKT, JNK/cJUN, Wnt/GSK-3β, and cell cycle pathways to exert its tumor-promoting or tumor-suppressing effect. The tissue expression level and methylation profiles of Eya4 can help predict the prognosis and anti-cancer treatment response among cancer patients. Targeting and altering Eya4 expression and activity could be a potential therapeutic strategy to suppress carcinogenesis. In conclusion, EYA4 may have both putative tumor-promoting and tumor-suppressing roles in different human cancers and has the potential to serve as a prognostic biomarker and therapeutic agent in various cancer types.

Matched MeSH terms: Genes, Tumor Suppressor
Fulltext Molecular mechanisms underlying the regulation of tumour suppressor genes in lung cancer

Lee JY, Bhandare RR, Boddu SHS, Shaik AB, Saktivel LP, Gupta G, et al.

Biomed Pharmacother, 2024 Apr;173:116275.
PMID: 38394846 DOI: 10.1016/j.biopha.2024.116275

Tumour suppressor genes play a cardinal role in the development of a large array of human cancers, including lung cancer, which is one of the most frequently diagnosed cancers worldwide. Therefore, extensive studies have been committed to deciphering the underlying mechanisms of alterations of tumour suppressor genes in governing tumourigenesis, as well as resistance to cancer therapies. In spite of the encouraging clinical outcomes demonstrated by lung cancer patients on initial treatment, the subsequent unresponsiveness to first-line treatments manifested by virtually all the patients is inherently a contentious issue. In light of the aforementioned concerns, this review compiles the current knowledge on the molecular mechanisms of some of the tumour suppressor genes implicated in lung cancer that are either frequently mutated and/or are located on the chromosomal arms having high LOH rates (1p, 3p, 9p, 10q, 13q, and 17p). Our study identifies specific genomic loci prone to LOH, revealing a recurrent pattern in lung cancer cases. These loci, including 3p14.2 (FHIT), 9p21.3 (p16INK4a), 10q23 (PTEN), 17p13 (TP53), exhibit a higher susceptibility to LOH due to environmental factors such as exposure to DNA-damaging agents (carcinogens in cigarette smoke) and genetic factors such as chromosomal instability, genetic mutations, DNA replication errors, and genetic predisposition. Furthermore, this review summarizes the current treatment landscape and advancements for lung cancers, including the challenges and endeavours to overcome it. This review envisages inspired researchers to embark on a journey of discovery to add to the list of what was known in hopes of prompting the development of effective therapeutic strategies for lung cancer.

Matched MeSH terms: Genes, Tumor Suppressor
Molecular genetic analysis of phosphatase and tensin homolog and p16 tumor suppressor genes in patients with malignant glioma

Abdullah JM, Zainuddin N, Sulong S, Jaafar H, Isa MN

Neurosurg Focus, 2003 Apr 15;14(4):e6.
PMID: 15679305

Several genes have been shown to carry mutations in human malignant gliomas, including the phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and p16 tumor suppressor genes. Alterations of this gene located on chromosome 10 q23 and 9p21, respectively, may contribute to gliomagenesis. In this study, the authors analyzed 20 cases of malignant gliomas obtained in patients living on the east coast of Malaysia to investigate the possibilities of involvement of the PTEN and p16 genes.

Matched MeSH terms: Genes, Tumor Suppressor/physiology
Long-term in vitro expansion of human adipose-derived stem cells showed low risk of tumourigenicity

Zaman WS, Makpol S, Sathapan S, Chua KH

J Tissue Eng Regen Med, 2014 Jan;8(1):67-76.
PMID: 22552847 DOI: 10.1002/term.1501

In the field of cell-based therapy and regenerative medicine, clinical application is the ultimate goal. However, one major concern is: does in vitro manipulation during culture expansion increases tumourigenicity risk on the prepared cells? Therefore, the aim of this study was to investigate the effect of long-term in vitro expansion on human adipose-derived stem cells (ASCs). The ASCs were harvested from lipo-aspirate samples and cultured until passage 20 (P20), using standard culture procedures. ASCs at P5, P10, P15 and P20 were analysed for morphological changes, DNA damage (Comet assay), tumour suppressor gene expression level (quantitative PCR), p53 mutation, telomerase activity, telomere length determination and in vivo tumourigenicity test. Our data showed that ASCs lost their fibroblastic feature in long-term culture. The population doubling time of ASCs increased with long-term culture especially at P15 and P20. There was an increase in DNA damage at later passages (P15 and P20). No significant changes were observed in both p53 and p21 genes expression throughout the long-term culture. There was also no p53 mutation detected and no significant changes were recorded in the relative telomerase activity (RTA) and mean telomere length (TRF) in ASCs at all passages. In vivo implantation of ASCs at P15 and P20 into the nude mice did not result in tumour formation after 4 months. The data showed that ASCs have low risk of tumourigenicity up to P20, with a total population doubling of 42 times. This indicates that adipose tissue should be a safe source of stem cells for cell-based therapy.

Matched MeSH terms: Genes, Tumor Suppressor
Fulltext Vast opportunity to study microrna (miRNA) in head and neck cancer among Malaysian population

Mohd. Arifin Kaderi, Kahairi Abdullah, Wan Ishlah Leman, Azmir Ahmad

International Journal of Allied Health Sciences, 2018;2(3):475-488.
MyJurnal

Head and neck cancer (HNC) is among the common cancer in Malaysia. Depending on the location of the cancer in head and neck region, each type of HNC has its own characteristics and prevalence to specific gender and ethnicity. The remote and inaccessible location of the cancer also cause the difficulty to detect the cancer. This make the cancer usually diagnosed at late stage and make the treatment very challenges and ended with low survival rate of post-treatment among HNC patients. In fact, the detection of HNC at early stage could promise high successful recovery rate. This situation demand lots of studies to explore the carcinogenesis of HNC and searching for robust diagnostic, prognostic and therapeutic biomarkers. MicroRNA (miRNA) is a class of non-coding RNA that regulate cellular physiology at post-transcriptional level. miRNAs expression has
been found to deregulate in various disease state, including cancer. A few studies revealed that miRNAs can behave as oncogenic and tumour suppressor in HNC. Even HNC is common in Malaysia, the studies of miRNA in HNC are still scarce. In this review article, we highlight the studies of miRNA in HNC that have been published by Malaysian researchers with aim to call more Malaysian researchers to focus on miRNA researches in HNC.

Matched MeSH terms: Genes, Tumor Suppressor
Progress in gene therapy treatments for prostate cancer

Xue J, Chen K, Hu H, Gopinath SCB

Biotechnol Appl Biochem, 2021 May 14.
PMID: 33988271 DOI: 10.1002/bab.2193

Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.

Matched MeSH terms: Genes, Tumor Suppressor
Fulltext Inverse correlation between P53 and Bcl-2 expression in breast carcinoma of Malaysian patients

Mdzin, R., Lau, T.Y., Rohaizak, M., Sharifah, N.A.

Medicine & Health, 2012;7(1):32-40.
MyJurnal

The tumour suppressor gene p53 and the proto-oncogene Bcl-2 encode respectively, for a nuclear phosphoprotein and for a mitochondrial membrane protein involved in multiple cellular functions. Both proteins are linked to programmed cell death pathways and provide prognostic information on breast carcinoma. Our aim is to study the expression of p53 and Bcl-2 oncoproteins in breast carcinoma and correlate with patients’ age, tumour size, disease stage and histological grade. Fifty nine cases of breast carcinomas from Universiti Kebangsaan Malaysia Medical Centre (UKMMC) were studied with the immunohistochemical method. Our results showed 45.8% (27 of 59) and 40.7% (24 of 59) of the breast carcinomas were immunopositive for p53 and Bcl-2 respectively. There was significant correlation between Bcl-2 expression with early tumour stage (p=0.01). No significant relationship was seen with other variables. Results also showed an inverse relationship between p53 and Bcl-2 expression (p=0.001). These findings indicate a down regulation of Bcl-2 by p53 in breast carcinogenesis.

Matched MeSH terms: Genes, Tumor Suppressor
Array comparative genomic hybridization analysis identified the chromosomal aberrations and putative genes involved in Prostate Tumorigenesis of Malaysian men

Nenny Noorina Saaid, Reena Rahayu Md Zin, Siti Aishah Md Ali, Sharifah Noor Akmal Syed Hussain, Zulkifli Zainuddin, Zubaidah Zakaria

Sains Malaysiana, 2014;43:1317-1326.

The identification of chromosomal aberrations in prostate cancer has been widely studied with several known oncogenes and tumor suppressor genes have successfully been discovered. The most frequent aberrations detected in western population were losses in chromosome 5q, 6q, 8p, 13q, 16q, 17p, 18q and gains of 7p/q and 8q. The purpose of this study was to determine the chromosomal aberrations among Malaysian men of Southeast Asia population and discover those potential genes within that chromosomal aberrant region. Thirty-six formalin-fixed paraffin embedded specimens consist of eight organ-confined prostate cancer cases, five with capsular invasion, 14 showed metastasis and nine cases had no tumor stage recorded, were analyzed by array CGH technique. Chromosomal losses were frequently detected at 4q, 6q, 8p, 13q, 18q while gains at 7q, 11q, 12p, 16q and 17q. Gain of 16q24.3 was statistically significant with tumor size. Gains of 6q25.1 and Xq12 as well as losses of 3p13-p1.2 and 13q33.1-q33.3 were significantly correlated with Gleason grade whereas 12p13.31 gain was associated with bone metastasis. Several potential genes have also been found within that aberrant region which is myopodin (4q26-q27), ROBO1 (3p13-p11.2), ERCC5 (13q33.1-q33.3) and CD9 (12p13.31), suggesting that these genes may play a role in prostate cancer progression. The chromosomal aberrations identified by array CGH analysis could provide important clues to discover potential genes associated with prostate tumorigenesis of Malaysian men.

Matched MeSH terms: Genes, Tumor Suppressor
Targeting oncogenes and tumor suppressors genes to mitigate chemoresistance

Fatemian T, Chowdhury EH

Curr Cancer Drug Targets, 2014;14(7):599-609.
PMID: 25308718

Malfunctions in membrane transporters or disruptions in signaling cascades induce resistance to chemotherapy in cancer cells resulting in treatment failure. To adjust the genetic alterations leading to these cellular protective measures, dissection and verification of the contributing routes would be required. In justification of knockdown of the key genes, RNA interference provides a reliable probing tool, enabling exploration of phenotypic manifestation of targeted genes. Investigation of the non-transporter targets, predominantly oncogenes and tumor suppressor genes, by means of small interfering RNA with the aim to re-sensitize cancer cells to therapeutics will be discussed in this review.

Matched MeSH terms: Genes, Tumor Suppressor/drug effects*
Fulltext Tumor suppressor role of miR-503

Gupta G, Chellappan DK, de Jesus Andreoli Pinto T, Hansbro PM, Bebawy M, Dua K

Panminerva Med, 2018 Mar;60(1):17-24.
PMID: 29164842 DOI: 10.23736/S0031-0808.17.03386-9

MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate post-transcriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR‑503, an associate of the "canonical" miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR‑503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR‑503 in different cancers and elaborate on its mechanism of action.

Matched MeSH terms: Genes, Tumor Suppressor*
Fulltext HOPX functions as a tumour suppressor in head and neck cancer

Yap LF, Lai SL, Patmanathan SN, Gokulan R, Robinson CM, White JB, et al.

Sci Rep, 2016 Dec 09;6:38758.
PMID: 27934959 DOI: 10.1038/srep38758

Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis.

Matched MeSH terms: Genes, Tumor Suppressor*
MicroRNA-based therapy and breast cancer: A comprehensive review of novel therapeutic strategies from diagnosis to treatment

Kaboli PJ, Rahmat A, Ismail P, Ling KH

Pharmacol Res, 2015 Jul;97:104-21.
PMID: 25958353 DOI: 10.1016/j.phrs.2015.04.015

MicroRNAs (miRNA) are 21-23 nucleotide molecules not translated into proteins that bind and target the 3' untranslated regions of mRNA. These characteristics make them a possible tool for inhibiting protein translation. Different cellular pathways involved in cancer development, such as cellular proliferation, apoptosis, and migration, are regulated by miRNAs. The objective of this review is to discuss various miRNAs involved in breast cancer in detail as well as different therapeutic strategies from the clinic to industry. A comprehensive discussion is provided on various miRNAs involved in breast cancer development, progression, and metastasis as well as the roles, targets, and related therapeutic strategies of different miRNAs associated with breast cancer. miRNAs known to be clinically useful for the diagnosis and prognosis of breast cancer are also discussed. Different strategies and challenges, including nucleic acid-based (miRNA mimics, antagomiRs, and miRNA sponges) and drug-based (drug resistance, drugs/miRNA interaction, nanodelivery, and sensing systems) approaches to suppress specific oncogenes and/or activate target tumor suppressors are discussed. In contrast to other articles written on the same topic, this review focuses on the therapeutic and clinical value of miRNAs as well as their corresponding targets in order to explore how these strategies can overcome breast cancer, which is the second most frequent type of cancer worldwide. This review focuses on promising and validated miRNAs involved in breast cancer. In particular, two miRNAs, miR-21 and miR-34, are discussed as the most promising targets for RNA-based therapy in non-invasive and invasive breast cancer, respectively. Finally, relevant and commercialized therapeutic strategies are highlighted.

Matched MeSH terms: Genes, Tumor Suppressor
P-TEFb goes viral

Zaborowska J, Isa NF, Murphy S

Inside Cell, 2016 04;1(2):106-116.
PMID: 27398404

Positive transcription elongation factor b (P-TEFb), which comprises cyclin-dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P-TEFb is required for productive elongation of transcription of protein-coding genes by RNA polymerase II (pol II). In addition, P-TEFb-mediated phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P-TEFb could be effective anti-viral agents.

Matched MeSH terms: Genes, Tumor Suppressor
Fulltext Thymoquinone, as a Novel Therapeutic Candidate of Cancers

Almajali B, Al-Jamal HAN, Taib WRW, Ismail I, Johan MF, Doolaanea AA, et al.

Pharmaceuticals (Basel), 2021 Apr 16;14(4).
PMID: 33923474 DOI: 10.3390/ph14040369

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.

Matched MeSH terms: Genes, Tumor Suppressor
Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells

Al-Jamal HAN, Johan MF, Mat Jusoh SA, Ismail I, Wan Taib WR

Asian Pac J Cancer Prev, 2018 Jun 25;19(6):1585-1590.
PMID: 29936783

Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in development and
progression of cancers. Re-expression of TSG is inversely proportionate with STAT3 signaling pathways.
Demethylation of DNA by 5-Azacytidine (5-Aza) results in re-expression of silenced TSG. Forced expression of
PRG2 by 5-Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor that potently inhibits BCR/
ABL tyrosine kinase resulting in hematological remission in CML patients. However, majority of CML patients treated
with imatinib would develop resistance under prolonged therapy. Methods: CML cells resistant to imatinib were
treated with 5-Aza and cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively.
Gene expression analysis was detected by real time-PCR, STATs activity examined using Western blot and methylation
status of PRG2 was determined by pyrosequencing analysis. Result: Expression of PRG2 was significantly higher in
K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreased
in K562-R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562-R+5-Aza cells which showed
higher sensitivity to imatinib. Conclusion: PRG2 gene is a TSG and its overexpression might induce sensitivity to
imatinib. However, further studies are required to evaluate the negative regulations of PRG2 on STAT3 signaling.

Matched MeSH terms: Genes, Tumor Suppressor
Fulltext miR-145 supports cancer cell survival and shows association with DDR genes, methylation pattern, and epithelial to mesenchymal transition

Manvati S, Mangalhara KC, Kalaiarasan P, Chopra R, Agarwal G, Kumar R, et al.

Cancer Cell Int, 2019;19:230.
PMID: 31516387 DOI: 10.1186/s12935-019-0933-8

Background: Despite several reports describing the dual role of miR-145 as an oncogene and a tumor suppressor in cancer, not much has been resolved and understood.
Method: In this study, the potential targets of miR-145 were identified bio-informatically using different target prediction tools. The identified target genes were validated in vitro by dual luciferase assay. Wound healing and soft agar colony assay assessed cell proliferation and migration. miR-145 expression level was measured quantitatively by RT-PCR at different stages of breast tumor. Western blot was used to verify the role of miR-145 in EMT transition using key marker proteins.
Result: Wound healing and soft agar colony assays, using miR-145 over-expressing stably transfected MCF7 cells, unraveled its role as a pro-proliferation candidate in cancerous cells. The association between miR-145 over-expression and differential methylation patterns in representative target genes (DR5, BCL2, TP53, RNF8, TIP60, CHK2, and DCR2) supported the inference drawn. These in vitro observations were validated in a representative set of nodal positive tumors of stage 3 and 4 depicting higher miR-145 expression as compared to early stages. Further, the role of miR-145 in epithelial-mesenchymal (EMT) transition found support through the observation of two key markers, Vimentin and ALDL, where a positive correlation with Vimentin protein and a negative correlation with ALDL mRNA expression were observed.
Conclusion: Our results demonstrate miR-145 as a pro-cancerous candidate, evident from the phenotypes of aggressive cellular proliferation, epithelial to mesenchymal transition, hypermethylation of CpG sites in DDR and apoptotic genes and upregulation of miR-145 in later stages of tumor tissues.

Matched MeSH terms: Genes, Tumor Suppressor
Absence of Ras, c-myc and Epidermal Growth Factor Receptor (EGFR) Mutations in Human Gliomas and its Clinical Factors Associated with Pathological Grading After Six Years of Diagnosis in North East Malaysian Patients

Ghazali MM, Mohd Zan MS, Yusof AA, Abdullah JM, Jaffar H, Ariff AR, et al.

Malays J Med Sci, 2005 Jul;12(2):27-33.
PMID: 22605955 MyJurnal

Neoplastic transformation appears to be a multi-step process in which the normal controls of cell proliferation and cell-cell interaction are lost, thus transforming normal cells into cancer. The tumorigenic process involves the interplay between oncogenes and tumour suppressor genes. In this study, we have selected the ras family, c-myc and epidermal growth factor receptor (EGFR) genes to detect whether their abnormalities are associated with the expression and progression of glioma cases in Malay patients. We have used the polymerase chain reaction-single stranded conformation polymorphism followed by direct sequencing for the study. For the ras gene family, we screened the point mutations in codons 12 and 61 of the H-, K-, and N-ras gene; for EGFR and c-myc, we analyzed only the exon 1 in glioma samples. In mutational screening analyses of the ras family, c-myc and EGFR gene, there was no mobility shift observed in any tumour analyzed. All patterns of single stranded conformation polymorphism (SSCP) band observed in tumour samples were normal compared to those in normal samples. The DNA sequencing results in all high-grade tumours showed that all base sequences were normal. All 48 patients survived after five years of treatment. In simple logistic regression analysis, variables which were found to be significant were hemiplegia (p=0.047) and response radiotherapy (p=0.003). Hemiplegics were 25 times more likely to have high pathological grade compared to those without. Patients with vascular involvement were 5.5 times more likely to have higher pathological grade. However, these findings were not significant in multivariate analysis. Patients who had radiotherapy were nearly 14 times more likely to have higher pathological grade. Multivariate analysis revealed that patients with hemiplegia were more likely to have higher pathological grade (p= 0.008). Those with higher pathological grading were 80 times more likely to have radiotherapy (p=0.004).

Matched MeSH terms: Genes, Tumor Suppressor
Association of p53 tumor suppressor gene with paraclinical and clinical modalities of gliomas patients in Malaysia

Yusoff AA, Abdullah J, Abdullah MR, Mohd Ariff AR, Isa MN

Acta Neurochir (Wien), 2004 Jun;146(6):595-601.
PMID: 15168228

Alteration of the tumor suppressor gene p53 is considered to be a critical step in the development of human cancer. Changes in this gene have been detected in a wide range of human tumours, including gliomas. In glioma, the presence of p53 gene alterations has been associated with worse prognosis.

Matched MeSH terms: Genes, Tumor Suppressor*
Loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in malays with malignant glioma

Zainuddin N, Jaafart H, Isa MN, Abdullah JM

Neurol Res, 2004 Jan;26(1):88-92.
PMID: 14977064

Recent advances in neuro-oncology have revealed different pathways of molecular oncogenesis in malignant gliomas including loss of heterozygosity on chromosomal regions harboring tumor suppressor genes. In the present study, we performed polymerase chain reaction-loss of heterozygosity (PCR-LOH) analysis using microsatellite markers to identify loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in the Malays with malignant gliomas. Of 12 cases with allelic losses, seven (58.3%) cases showed LOH on chromosome 10q, three (25.0%) cases showed LOH on chromosome 9p, four (33.3%) cases showed LOH on chromosome 17p and two (16.7%) cases showed LOH on chromosome 13q. The cases include five (41.7%) cases of glioblastoma multiforme, three (25.0%) cases of anaplastic astrocytoma, three (25.0%) cases of anaplastic oligodendroglioma and one (8.3%) case of anaplastic ependymoma. Four cases showed loss of heterozygosity on more than one locus. Our findings showed that loss of heterozygosity on specific chromosomal regions contributes to the molecular pathway of glioma progression in Malay population. In addition, these data provide useful evidence of molecular genetic alterations of malignant glioma in South East Asian patients, particularly in the East Coast of Malaysia.

Matched MeSH terms: Genes, Tumor Suppressor/physiology
Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population

Ashazila MJ, Kannan TP, Venkatesh RN, Hoh BP

Oral Oncol, 2011 May;47(5):358-64.
PMID: 21450513 DOI: 10.1016/j.oraloncology.2011.03.005

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been documented as important events in oral squamous cell carcinoma (OSCC). Five microsatellite markers D3S192, D3S966, D3S647, D3S1228 and D3S659 were selected on chromosome 3p because of high frequency of alterations reported in head and neck squamous cell carcinoma and the involvement of von Hippel Lindau (VHL) at 3p25-26 and the fragile histidine triad (FHIT) at 3p14.2 genes proven in many tumour types. A total of 50 archival tissue samples of OSCC and corresponding normal samples were analyzed for LOH and MSI status. The overall LOH for the markers selected on 3p was 56 out of 189 informative cases (29.6%). The most frequent LOH was identified for the marker D3S966 which was 18/42 (42.8%) of informative cases suggesting the presence of putative tumour suppressor genes (TSGs) in this loci. In this study, high frequency of microsatellite instability was found in D3S966 which was 28.6% of informative cases; this reveals the possibility of mutations of MMR genes in this region. Frequent microsatellite alterations (MA) were observed in 3 markers D3S966 (71.4%), D3S1228 (56.7%) and D3S192 (41.0%). There was no significant association between LOH with gender, tumour stages and differentiation grades. However, there was a significant association between tumour stage and differentiation grades with MSI status in OSCC in Malaysian population with p values of 0.002 and 0.035, respectively. There was also a significant association between MA and differentiation grades (p=0.041).

Matched MeSH terms: Genes, Tumor Suppressor

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