scholarly journals Microsatellite Instability and Loss of Heterozygosity of Tumor Suppressor Genes in Bosnian Patients with Sporadic Colorectal Cancer

2008 ◽  
Vol 8 (4) ◽  
pp. 313-321
Author(s):  
Vesna Hadžiavdić ◽  
Nada Pavlović-Čalić ◽  
Izet Eminović
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Microsatellite Instability ◽  
Tumor Suppressor Genes ◽  
Genetic Alterations ◽  
Sporadic Colorectal Cancer ◽  
Tumor Type ◽  
Suppressor Genes ◽  
Amsterdam Criteria ◽  
Surrounding Healthy Tissue

Considering its frequency, high mortality rate as well as many etiological mysteries colorectal cancer is a challenge to contemporary science. In our study we analyzed RER + and RER - phenotypes and their relations with clinical-pathological characteristics of sporadic colorectal cancers. We also analyzed genetic alterations of tumor suppressor genes as well as their relation with microsatellite instability. The study was based on 54 tumor samples and 54 samples of the surrounding healthy tissue of patients with colorectal cancer. According to Amsterdam Criteria and Bethesda Criteria 35/54 or 64,81% belonged in the group of sporadic colorectal cancer. Mononucleotide marker Bat 25 showed instability in 48,57%; Bat 26 in 45,71% and Bat 40 in 29/35 82,86% of tumor samples. Considering dinucleotide markers, TP 53 showed instability in 54,29% and DS123 in 37,14% of tumor samples. Genetic alterations in tumor suppressor genes were found in tumor tissue: NM 23 in 54,29% samples, p53 in 51,43%, APC in 51,43%, DCC2 in 34,29%, RB1 in 22, 86% and DCC 1 in 28,57%. Our studies confirmed that genetic instability had an important role in the development of tumor type. Our results showed that mononucleotide marker Bat 40 might be used for an easy and fast screening procedure in Bosnian population, because it exhibited high percent of microsatellite instability and was in relation with RER+ phenotype. This investigation showed that different genetic alterations may occur during cancer development in each individual patient’s tumor. These changes result in MMR inactivation, which causes RER+ phenotype. Our results suggest a connection between alteration in some tumor suppressor genes and MSI phenotype of sporadic colorectal cancer in Bosnian population.

scholarly journals Screening of tumor suppressor genes on 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer

2008 ◽  
Vol 121 (24) ◽  
pp. 2479-2486 ◽  
Author(s):  
Chong-zhi ZHOU ◽  
Guo-qiang QIU ◽  
Xiao-liang WANG ◽  
Jun-wei FAN ◽  
Hua-mei TANG ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Chinese Patients ◽  
Sporadic Colorectal Cancer ◽  
Suppressor Genes

Methylation Profiles of Tumor Suppressor Genes in Inflammatory Bowel Disease-Associated and Sporadic Colorectal Cancer: A Comparison

2011 ◽  
Vol 140 (5) ◽  
pp. S-349
Author(s):  
Marian M. Claessen ◽  
Frank P. Vleggaar ◽  
Marguerite E. Schipper ◽  
John W. Hinrichs ◽  
Remco D. Radersma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Tumor Suppressor ◽  
Bowel Disease ◽  
Tumor Suppressor Genes ◽  
Sporadic Colorectal Cancer ◽  
Suppressor Genes ◽  
Inflammatory Bowel

Current Understanding of Epigenetics Driven Therapeutic Strategies in Colorectal Cancer Management

2021 ◽  
Vol 21 ◽  
Author(s):  
Dikshita Deka ◽  
Marco Scarpa ◽  
Alakesh Das ◽  
Surajit Pathak ◽  
Antara Banerjee
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Suppressor ◽  
Epithelial Cells ◽  
Tumor Suppressor Genes ◽  
Genetic Alterations ◽  
Primary Role ◽  
Suppressor Genes ◽  
Cancer Management ◽  
Cancer Pathogenesis

: Colorectal cancer is known to be the paramount reason for cancer deaths around the globe. It occurs due to the aggregation of epigenetic and genetic alterations in colon epithelial cells that transmute them into adenocarcinomas. Epigenetic mechanisms are interpreted as the changes in expression of the gene which is not associated with the alterations in the principal DNA sequence, while genetic changes involve modifications in oncogenes and tumor suppressor genes. The changes in the epigenetic in colon cancer that transmute colonic epithelial cells include chromatin modifications, microRNA expression, telomere length, and DNA methylation. DNA hypermethylation causes down-regulation and unsuitable expression of specific microRNA which can behave like tumor suppressor genes. Histone modifications can also influence the chromatin remodeling and the gene expression, hence performs an eminent function in silencing of the gene in colon cancer. Moreover, the telomere/telomerase interaction is a prime mechanism to embrace both cellular replicative potential and genomic instability and its malfunction plays a primary role in colon cancer. Deducing the genesis and the function of epigenetic abnormality in colon cancer pathogenesis will head to a potent prevention and therapeutic approach for colon cancer patients. Epigenetic drugs which emphasizes the convertible essence of epigenetic occurrences have accompanied the probability of epigenetic approach as a treatment alternative in colon cancer. Hence, this review is undertaken to critically envelop the recent advance events in colorectal cancer therapies with a special emphasis on remedies targeting epigenetic modulators and future challenges towards therapeutic interventions.

scholarly journals Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer

2015 ◽  
Vol 36 (10) ◽  
pp. 1103-1110 ◽  
Author(s):  
Keyvan Torabi ◽  
Rosa Miró ◽  
Nora Fernández-Jiménez ◽  
Isabel Quintanilla ◽  
Laia Ramos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Uniparental Disomy ◽  
Suppressor Genes

Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer

1992 ◽  
Vol 12 (3) ◽  
pp. 1387-1395
Author(s):  
M C Goyette ◽  
K Cho ◽  
C L Fasching ◽  
D B Levy ◽  
K W Kinzler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Loss Of Function ◽  
Chromosome 18 ◽  
Chromosome 5 ◽  
Suppressor Genes ◽  
Single Defect

Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.

scholarly journals The co-regulatory networks of tumor suppressor genes, oncogenes, and miRNAs in colorectal cancer

2017 ◽  
Vol 56 (11) ◽  
pp. 769-787 ◽  
Author(s):  
Martha L. Slattery ◽  
Jennifer S. Herrick ◽  
Lila E. Mullany ◽  
Wade S. Samowitz ◽  
John R. Sevens ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Regulatory Networks ◽  
Suppressor Genes

Aberrant Gene Promoter Methylation of Tumor Suppressor Genes in Plasma Cell Disorders.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2487-2487
Author(s):  
Carmen Stanganelli ◽  
Jorge Arbelbide ◽  
Juliana Zimerman ◽  
Dorotea Beatriz Fantl ◽  
Claudia Corrado ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Peripheral Blood ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Genetic Alterations ◽  
Negative Regulator ◽  
Epigenetic Mechanism ◽  
Gene Methylation ◽  
Suppressor Genes ◽  
Number Of Genes

Abstract There is increasing evidence that, in addition to genetic aberrations, epigenetic processes play a major role in carcinogenesis. Particularly, hypermethylation of CpG islands of the promoter regions of tumor suppressor genes (TSG) is now considered as an important epigenetic mechanism for gene inactivation. Multiple myeloma (MM) is characterized by neoplastic proliferation of monoclonal plasma cells. The natural course of disease may progress through monoclonal gammopathy of undetermined significance (MGUS) to MM. During this process, multiple genetic alterations are sequentially acquired and aberrant promoter hypermethylation might be one of the steps involved in this progression. In this study, we have evaluated methylation status of the following TSG: p15INK4b, p16INK4a, p14ARF, SOCS-1, p27KIP1, RASSF1A and p73 genes, in order to determine if they were involved in the evolution of MGUS to MM. Forty four MM (21 males; mean age 67.5 years; Durie-Salmon clinical stages: I: 20%, II:14% and III: 66%) and 21 MGUS patients (6 males; mean age 68 years) were study. All patients gave informed consent and the study was approved by the Ethics Committee of our Institution. Peripheral blood samples from 10 normal individuals and CpGenome Universal Methylated DNA (Chemicon International) were used as negative and positive controls, respectively. DNA was extracted from bone marrow cells of patients and peripheral blood lymphocytes of controls using phenol/chloroform method. Methylation status was performed using Methylation Specific PCR (MSP) technique. For statistical analysis, Student t and Fisher exact tests were used. The methylation index (MI; ratio between the number of genes methylated and the number of genes analyzed) was also calculated. SOCS-1 gene methylation was significantly more frequent in MM (52%) than in MGUS patients (14%) (p=0,006). Frequencies of methylation of p14ARF, p15INK4b, p16INK4a and RASSF1A were comparable in both entities: 29%, 32%, 7% and 2%, respectively, for MM; and 29%, 29%, 5% and 0%, respectively, for MGUS. TP73 gene showed a tendency of higher methylation in MM (45%) than in MGUS (33%). All patients lacked methylation at p27KIP1 gene. Whereas the percentage of MM with at least one gene methylated (84%) did not showed differences to that of MGUS (66%), the mean MI of MGUS was lower (0.16; range 0.14-0.43) than that of MM (0.24; range 0.14-0.71) (p<0.05). None of the target genes were methylated in normal samples. No statistical significant correlation with clinical characteristics: gender, age, isotype, level of M-component, type of light chain, stage of the disease, haemoglobin, serum albumin level, calcium, β2 microglobulin and LDH, were observed. To our knowledge, this is the first report of methylation in MM and MGUS from Argentina. The similar frequency of p14ARF, p15INK4b, p16INK4a and RASSF1A gene methylation observed in MM and MGUS would suggest that they are probably not involved in the progression of MGUS. However, SOCS1 gene methylation was significantly more frequent in MM than in MGUS suggesting that methylation of this gene might be involved in clonal evolution of MGUS to MM. SOCS1 is a negative regulator of cytokine signaling, being important in normal lymphocyte development and differentiation. Silencing of SOCS1 may result in greater responsiveness to cytokines, which may favour the neoplastic development.

scholarly journals Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1781-1787 ◽  
Author(s):  
G Gaidano ◽  
RS Hauptschein ◽  
NZ Parsa ◽  
K Offit ◽  
PH Rao ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Suppressor Genes ◽  
Molecular Evidence ◽  
Low Grade ◽  
Chromosome 6 ◽  
Tumor Type ◽  
Suppressor Genes ◽  
Non Hodgkin Lymphoma

Abstract The recurrent loss of genetic material from a specific chromosomal region in a given tumor type suggests the presence of a tumor- suppressor gene, the loss or inactivation of which may be relevant for tumorigenesis. In this study, we provide molecular evidence for the recurrent association between deletions on the long arm of chromosome 6 and B-cell non-Hodgkin lymphoma (B-NHL). Normal and tumor DNAs from 71 cases of B-NHL were studied for loss of constitutional heterozygosity (LOH) at 19 loci on chromosome 6 using a panel of restriction fragment length polymorphism (RFLP) probes. LOH, indicating deletion of all or part of 6q, was detected in 16 of 71 cases (22.5%), ranging from low- grade to high-grade B-NHL. The isolated loss of 6p or the loss of other chromosomes (8, 17, 22) tested as controls for specificity was not observed in any case. Comparison of the extent of the deletions among different cases allowed the identification of two distinct regions of minimal deletion (RMD) at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD- 2), respectively, suggesting the existence of two tumor-suppressor genes. These data support a role for 6q deletions in B-NHL pathogenesis and provide a basis for identifying the corresponding tumor-suppressor genes.

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