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1.
Background
The question of whether “recurrent” laryngeal carcinoma is truly a new tumour with a clonal origin that differs from that of the primary tumour has remained unanswered. The objective of this study was to determine whether recurrent tumours have the same genetic basis as primary tumours, as the answer to this question is important for the development of treatment strategies.Materials and Methods
Matched samples consisting of primary tumour, recurrent tumour and normal tissue were obtained from the same patient. A total of 37 patients with laryngeal cancer were examined for loss of heterozygosity (LOH) on the 3p, 5p, 7q, 8p, 9p, 13p, 17p and 18q chromosomal arms using PCR to amplify microsatellite markers. All patients were routinely followed up and 5-year survival rates were calculated using directly calculating method and Kaplan-Meier''s method.Results
A total of 28 out of 37 (75.6%) patients showed LOH at a minimum of one locus, and 19 out of 37 (51.3%) patients showed LOH at two loci. Primary and recurrent tumours in each patient showed identical allelic loss patterns and incidence rates. Patients without LOH had a longer average time to recurrence than patients with LOH (P<0.05). Additionally, patients with LOH had a longer average smoking duration prior to surgery than patients without LOH (P<0.05). The 5-year survival rates were 32.14%in patients with LOH versus 44.4% in patients without LOH.Conclusions
The data indicate that primary and recurrent tumours have the same clonal origin. This result implies that we failed to radically resect the primary tumours and/or micrometastases in these patients. Consequently, some form of adjunctive therapy may be necessary. Additionally, the data indicate that the recurrence of laryngeal squamous cell carcinoma is closely related to chromosomal aberrations (specifically LOH). 相似文献2.
Ying Liu Phillippa Dodds Gracy Emilion Andrew J Mungall Ian Dunham Stephan Beck Spencer R Wells L F Mark Charnock Trivadi S Ganesan 《BMC genetics》2002,3(1):20-20
Background
In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To identify the putative tumour suppressor gene, we established a physical map initially with YACs and subsequently with PACs/BACs from D6S264 to D6S149 . To accelerate the identification of genes, we sequenced the entire contig of approximately 1.1 Mb. Seven genes were identified within the region of allele loss between D6S264 and D6S149 . 相似文献3.
4.
Carlos Aya-Bonilla Emily Camilleri Larisa M Haupt Rod Lea Maher K Gandhi Lyn R Griffiths 《BMC genomics》2014,15(1)
Background
The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis.Results
Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL.Conclusions
The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.Electronic supplementary material
The online version of this article (doi: 10.1186/1471-2164-15-390) contains supplementary material, which is available to authorized users. 相似文献5.
Neill Patani Anthony Douglas-Jones Robert Mansel Wen Jiang Kefah Mokbel 《Cancer cell international》2010,10(1):29
Introduction
Melanoma differentiation associated gene-7 (MDA-7), also known as interleukin (IL)-24, is a tumour suppressor gene associated with differentiation, growth and apoptosis. However, the mechanisms underlying its anti-neoplastic activity, tumour-specificity and efficacy across a spectrum of human cancers have yet to be fully elucidated. In this study, the biological impact of MDA-7 on the behavior of breast cancer (BC) cells is evaluated. Furthermore, mRNA expression of MDA-7 is assessed in a cohort of women with BC and correlated with established pathological parameters and clinical outcome. 相似文献6.
7.
GL Huang BK Li MY Zhang RR Wei YF Yuan M Shi XQ Chen L Huang HZ Zhang W Liu BJ Huang H Li XF Zheng XR Luo HY Wang 《PloS one》2012,7(8):e44061
Objectives
The role of heparanase (HPSE) gene in cancers including hepatocellular carcinoma (HCC) is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC.Methods
The HPSE gene was studied in three different aspects: (1) loss of heterozygosity (LOH) by a custom SNP microarray and DNA copy number by real-time PCR; (2) mRNA level by qRT-PCR; and (3) protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed.Results
Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111) of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112) of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80) of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients.Conclusions
The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients. 相似文献8.
9.
Johan Staaf Johan Vallon-Christersson David Lindgren Gunnar Juliusson Richard Rosenquist Mattias Höglund Åke Borg Markus Ringnér 《BMC bioinformatics》2008,9(1):409
Background
Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples. 相似文献10.
Background
Allelic-loss studies record data on the loss of genetic material in tumor tissue relative to normal tissue at various loci along the genome. As the deletion of a tumor suppressor gene can lead to tumor development, one objective of these studies is to determine which, if any, chromosome arms harbor tumor suppressor genes. 相似文献11.
Wijnhoven SW Kool HJ van Teijlingen CM van Zeeland AA Vrieling H 《Mutation research》2001,473(1):23-36
Loss of heterozygosity (LOH) of tumour suppressor genes is a crucial step in the development of sporadic and hereditary cancer. Recently, we and others have developed mouse models in which the frequency and nature of LOH events at an autosomal locus can be elucidated in genetically stable normal somatic cells. In this paper, an overview is presented of recent studies in LOH-detecting mouse models. Molecular mechanisms that lead to LOH and the effects of genetic and environmental variables are discussed. The general finding that LOH of a marker gene occurs frequently in somatic cells of the mouse without deleterious effects on cell viability, suggests that also tumour suppressor genes are lost in similar frequencies. LOH of tumour suppressor genes may thus be an initiating event in cancer development. 相似文献
12.
Kelly J Langford Jon M Askham Tracy Lee Matthew Adams Ewan E Morrison 《BMC cell biology》2006,7(1):3-18
Background
The trafficking of the adenomatous polyposis coli (APC) tumour suppressor protein in mammalian cells is a perennially controversial topic. Immunostaining evidence for an actin-associated APC localisation at intercellular junctions has been previously presented, though live imaging of mammalian junctional APC has not been documented. 相似文献13.
Although the occurrence of bladder cancer is common, the molecular events underlying the pathogenesis of this cancer remain ill-defined. A loss of heterozygosity (LOH) at specific chromosomal loci may predispose individuals to the development of bladder cancer but this has not been examined in detail. Furthermore, the role that deletion or inactivation of putative tumour suppressor genes might play in the genesis of bladder cancer has not been established. In this study, allelic deletion analysis on the short arm of chromosome 17 of patients with primary bladder tumours failed to show deletion at 17p13 (0/7), a region known to contain the p53 tumour suppressor gene. Chromosome 11p15 showed allelic deletion at the IGF2 locus (2/7: 29%) and the PTH locus (1/11: 9%). However, no deletion was observed at the CALCA locus (0/6). LOH at 11p13, a region containing the Wilm's tumour suppressor gene (WT1), was also studied. Analysis of LOH at 11p13 showed deletion at the CAT locus (13/18: 72%), the J/D11S414 locus (5/15: 33%), the WT1 locus (7/14: 50%) and the FSHB locus (6/16: 38%). The significance of these findings is discussed. 相似文献
14.
Paul A. Crossey Keith Foster Frances M. Richards Maude E. Phipps Farida Latif Kalman Tory Michael H. Jones Elizabeth Bentley Ram Kumar Michael I. Lerman Bert Zbar Nabeel A. Affara Malcolm A. Ferguson-Smith Eamonn R. Maher 《Human genetics》1994,93(1):53-58
Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumours. The VHL disease gene maps to chromosome 3p25-p26. To investigate the mechanism of tumourigenesis in VHL disease, we analysed 24 paired blood/tumour DNA samples from 20 VHL patients for allele loss on chromosome 3p and in the region of tumour suppressor genes on chromosomes 5, 11, 13, 17 and 22. Nine out of 24 tumours showed loss of heterozygosity (LOH) at at least one locus on chromosome 3p and in each case the LOH included the region to which the VHL gene has been mapped. Chromosome 3p allele loss was found in four tumour types (RCC, haemangioblastoma, phaeochromocytoma and pancreatic tumour) suggesting a common mechanism of tumourigenesis in all types of tumour in VHL disease. The smallest region of overlap was between D3S1038 and D3S18, a region that corresponds to the target region for the VHL gene from genetic linkage studies. The parental origin of the chromosome 3p25-p26 allele loss could be determined in seven tumours from seven familial cases; in each tumour, the allele lost had been inherited from the unaffected parent. Our results suggest that the VHL disease gene functions as a recessive tumour suppressor gene and that inactivation of both alleles of the VHL gene is the critical event in the pathogenesis of VHL neoplasms. Four VHL tumours showed LOH on other chromosomes (5q21, 13q, 17q) indicating that homozygous VHL gene mutations may be required but may not be sufficient for tumourigenesis in VHL disease. 相似文献
15.
Micheline Giphart-Gassler Arnolda De Nooij-Van Dalen Vera Van Buuren-Van Seggelen Bruno Morolli Paul Lohman Hanneke Kluin-Nelemans 《Mutation research》1998,400(1-2):409-419
A search was initiated towards the localization of novel mutated tumour suppressor genes that may be involved in adult leukaemia. For this purpose, we measured the occurrence of loss of heterozygosity (LOH) in nine patients with acute B-lineage leukaemia (ALL) and one with undifferentiated leukaemia (AUL). Eight leukaemias exhibited a diploid karyotype. For each patient, PCR products of 130 polymorphic microsatellite markers, located in subtelomeric areas of every autosomal chromosome arm were analysed to visualize LOH events resulting from reduplication of a single mutated chromosome or from mitotic recombination. These kinds of LOH events contribute most to LOH in model systems but cannot be detected by classical cytogenetic techniques. By comparing allelic PCR products in tumour cells with those in normal cells, LOH was found in tumour cells of one ALL patient at 9p which harbours the known p16INK44 tumour suppressor gene. In the AUL patient, however, LOH was detected at the telomeres of 4q and 21q, suggesting that these sites may contain novel tumour suppressor genes specifically involved in this form of leukaemia. In the DNA of tumour cells from eight out of 10 patients no LOH was detected. This is in contrast with the general assumption that LOH is a frequent phenomenon in ALL. However, some markers at telomeric regions of chromosomes were already homozygous in the control T-cells of several patients. For instance, we found in the DNA of control cells from one patient five consecutive microsatellites on 9p up to 9p43 which were homozygous and in three other patients homozygosity was observed in band 8q24, which includes the MYC gene. These observations indicate that LOH events already are present in non-cancerous putative stem cells and that mitotic recombination may be a very early event in leukaemogenesis. 相似文献
16.
Background
EB1 is a microtubule tip-associated protein that interacts with the APC tumour suppressor protein and the p150glued subunit of dynactin. We previously reported that an EB1 deletion mutant that retains both of these interactions but does not directly associate with microtubules (EB1-ΔN2-GFP) spontaneously formed perinuclear aggregates when expressed in COS-7 cells. 相似文献17.
18.
Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion through miR‐181a
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Zhiwen Ba Lili Gu Songnan Hao Xiaofang Wang Zhenping Cheng Guangchen Nie 《Cell proliferation》2018,51(1)
Objectives
Long non‐coding RNA cancer susceptibility candidate 2 (CASC2) is a novel lncRNA and has been indicated as playing tumour suppressor gene in several tumours. However, the role of CASC2 in osteosarcoma is still uncovered.Materials and methods
The CASC2 and miR‐181a expressions were measured via qRT‐PCR. CCK‐8 assay and colony formation assay were performed to determine the cell growth, and transwell assay was performed to assess the cell invasion.Results
We showed that CASC2 expression was downregulated in osteosarcoma samples and cell lines. Moreover, we showed that downregulated expression of CASC2 was correlated with advanced TNM stage. Furthermore, overexpression of CASC2 inhibited osteosarcoma cell proliferation, colony formation, and invasion. In addition, we indicated that ectopic expression of CASC2 suppressed miR‐181a expression and enhanced the expression of Ras association domain family member 6 (RASSF6), PTEN and ATM in osteosarcoma cell, which were the direct target gene of miR‐181a. Moreover, we indicated that RASSF6 expression was downregulated in osteosarcoma samples and cell lines and downregulated expression of RASSF6 was correlated with advanced TNM stage. We found that the expression of RASSF6 was positively correlated with the expression of CASC2 in osteosarcoma tissues. Ectopic expression of CASC2 suppressed the osteosarcoma cell proliferation, colony formation and invasion through regulating RASSF6 expression.Conclusions
Our data illuminated that CASC2 acted as a tumour suppressor in osteosarcoma progression. 相似文献19.
Background
The identification of known mutations in a cell population is important for clinical applications and basic cancer research. In this work an immobilized form of the polymerase chain reaction, referred to as polony technology, was used to detect mutations as well as gene deletions, resulting in loss of heterozygosity (LOH), in cancer cell lines. Specifically, the mutational hotspots in p53, namely codons 175, 245, 248, 249, 273, and 282, and K-ras2, codons 12, 13 and 61, were genotyped in the pancreatic cell line, Panc-1. In addition LOH analysis was also performed for these same two genes in Panc-1 by quantifying the relative gene copy number of p53 and K-ras2. 相似文献20.
Liane M. McGlynn Simon McCluney Nigel B. Jamieson Jackie Thomson Alasdair I. MacDonald Karin Oien Euan J. Dickson C. Ross Carter Colin J. McKay Paul G. Shiels 《PloS one》2015,10(6)