High‐resolution loss of heterozygosity screening implicates <i>PTPRJ</i> as a potential tumor suppressor gene that affects susceptibility to non‐hodgkin's lymphoma

Aya-Bonilla, Carlos; Green, Michael R.; Camilleri, Emily T.; Benton, Miles C.; Keane, Colm; Marlton, Paula; Lea, Rodney Arthur; Gandhi, Maher K.; Griffiths, Lyn R.

doi:10.1002/gcc.22044

Cited by 20 publications

(45 citation statements)

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“…In order to determine whether the candidate tumour suppressor genes (TSGs) located within common LOH regions across DLBCL and FL cases interact and participate within common cellular networks, a global interactome of a total of 262 genes affected by LOH events [8], was created using the VisANT (v. 4.06) platform (Figure 1). As a result of this analysis, the METABOLIC pathway (KEGG hsa-01100) was identified as the most enriched pathway by these candidate TSGs.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, in a recent study, using a high resolution loss of heterozygosity (LOH) analysis in FLs and DLBCLs, we also identified candidate tumour suppressor genes (TSGs) within common LOH regions across these NHL subtypes and implicated them in the lymphomagenesis of these B-cell lymphomas [8]. In this study, we have performed pathway analysis of these candidate TSGs, in order to identify common cellular networks that might be altered by the inactivation of one or more TSGs in the lymphomagenesis of these B-cell lymphomas.…”

Section: Introductionmentioning

confidence: 99%

“…LOH of PTPRJ was also confirmed by a decrease of heterozygosity of a microsatellite targeting PTPRJ loci in these NHL cases. In addition, FL cases with LOH exhibited a significant downregulation of PTPRJ [8]. Several lines of evidence support the tumour suppressive role of PTPRJ , as this protein tyrosine phosphatase has been implicated in the oncogenesis of breast, lung, colorectal, thyroid and meningioma cancers [9–12].…”

Section: Introductionmentioning

confidence: 99%

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In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

et al. 2014

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BackgroundThe 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.ResultsPathway 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.ConclusionsThe 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 materialThe online version of this article (doi: 10.1186/1471-2164-15-390) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

et al. 2014

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“…Also the LOH of PTPRJ connected with its downregulation has been suggested to be a common mechanism in Non-Hodgkin's lymphoma genesis (17). The lower PTPRJ expression both on mRNA and protein levels was also reported in esophageal squamous cell carcinoma (ESCC) compared to normal cells.…”

Section: Discussionmentioning

confidence: 99%

Customized Array Comparative Genomic Hybridization Analysis of 25 Phosphatase-encoding Genes in Colorectal Cancer Tissues

Łaczmańska

Skiba

Karpiński

et al. 2017

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Abstract. Background The role of protein tyrosine phosphatases (PTPs) is widely described in both normal and cancer tissues. PTPs play an important role in many cellular pathways, co-acting with protein kinases via phosphorylation and dephosphorylation in activation and deactivation of a variety of enzymes. Therefore, their impact on cancer development and progression seems undeniable (1). To date the role of PTPs functioning mainly as tumour suppressor genes has been described in many cancers, such as colorectal, gastric, breast, ovarian, cervical, pancreatic, prostate, thyroid and many others (2). Colorectal cancer (CRC) is one of the common causes of cancer-related deaths and therefore is once of the most intensively studied types (1, 3). Thus, it has been proven that genetic pathways that are altered during CRC development and progression involve genes regulated to cell growth and differentiation, apoptosis and other processes crucial for cell homeostasis (2). Major genetic mechanisms underlying either hereditary or sporadic CRC are well known, but intensive studies on molecular mechanisms influencing CRC development and progression are still ongoing. CRC is characterized by chromosomal instability, loss of heterozygosity, microsatellite instability, multiple gene mutations and also epigenetic alterations, making CRC an extremely heterogeneous disease (3).Protein tyrosine phosphatases were also revealed as being altered in CRCs. While searching for molecular mechanisms of these alterations, chromosomal aberrations (deletions/ duplications of whole regions including PTPs), gene mutations (small intragenic deletions, point mutations), and epigenetic deregulation (promoter hypermethylation) have been observed (1,2,(4)(5)(6).The PTP superfamily is divided into four families depending on the amino acid sequence in their catalytic domain (1). Receptor PTPs (RPTPs), non-receptor PTPs (NRPTPs) and dual specificity phosphatases (DUSPs) that can dephosphorylate not only tyrosine but also serine and threonine residues belong to the largest class (class I), possessing a cysteine residue in their catalytic centre. Moreover, cell division cycle 14 (Cdc14) (serine and threonine specific), MAP kinase phosphatases (MPKs), slingshots (serine specific) as well as phosphatase and tensin homologs (PTENs) and myotubularins (both D3-phosphoinositide specific) are also included in this class (1). 69This article is freely accessible online.Correspondence to:

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“…It has been elucidated that suppression of PTPRO by promoter methylation could contribute to the augmented phosphorylation and constitutive activity of its substrate BCR/ABL1 [105]. Loss of heterozygosity has been reported to be related to PTPRK [106] and PTPRJ [107] in lymphoma. Both are presented as putative tumor suppressor genes [108,109], the inactivation of which induced by loss of heterozygosity, plays roles in neoplasia.…”

Section: • Receptor Protein Tyrosine Phosphatases and Duspsmentioning

confidence: 99%

Mutations in Tyrosine Kinase and Tyrosine Phosphatase and their Relevance to the Target Therapy in Hematologic Malignancies

et al. 2015

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Protein tyrosine kinases and protein tyrosine phosphatases play pivotal roles in regulation of cellular phosphorylation and signal transduction with opposite functions. Accumulating evidences have uncovered the relevance of genetic alterations in these two family members to hematologic malignancies. This review underlines progress in understanding the pathogenesis of these genetic alterations including mutations and aberrant expression and the evolving protein tyrosine kinases and protein tyrosine phosphatases targeted therapeutic strategies in hematologic neoplasms.

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High‐resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non‐hodgkin's lymphoma

Cited by 20 publications

References 55 publications

In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Customized Array Comparative Genomic Hybridization Analysis of 25 Phosphatase-encoding Genes in Colorectal Cancer Tissues

Mutations in Tyrosine Kinase and Tyrosine Phosphatase and their Relevance to the Target Therapy in Hematologic Malignancies

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