Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B‐cell lymphoma and multiple myeloma

Baccon, Patricia Le; Leroux, Dominique; Dascalescu, Christina; Duley, Samuel; Marais, Danielle; Esmenjaud, Eliane; Sotto, J. J.; Callanan, Mary

doi:10.1002/gcc.1189

Cited by 88 publications

(89 citation statements)

References 62 publications

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“…16,[19][20][21][22][23][24] The molecular structure of the t(8;14;18) rearrangement has been studied in detail in the cell lines DOHH2, VAL and ROS-50. 5 These studies have demonstrated that concurrent deregulation of BCL2 and MYC was achieved by translocation with a single IGH allele, whereby separation of the 3 0 and 5 0 IGH enhancer elements occurs with relocation of the BCL2-5 0 IGH enhancer fusion to the der (8), and translocation of MYC adjacent to the 3 0 IGH enhancer element that is retained on the der (14).…”

Section: Discussionmentioning

confidence: 99%

Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas

et al. 2005

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B-cell leukaemia or lymphoma with a combination of t(8;14)(q24;q32) of Burkitt leukaemia/lymphoma and t(14;18)(q32;q21) of follicular lymphoma may present clinically as de novo acute lymphoblastic leukaemia or transformation of follicular lymphoma to aggressive histology diffuse lymphoma. A number of cell lines have been reported with a complex t(8;14;18) with fusion of MYC, IGH and BCL2 on the same derivative 8 chromosome. The objective of this study was to determine the frequency and chromosomal features of this der(8)t(8;14;18) in a series of acute leukaemias and malignant lymphomas. A database of 1350 leukaemia and lymphoma karyotypes was searched for cases with structural alterations affecting both 8q24 and 18q21. A total of 55 cases were identified, of which eight revealed a complex der(8)t(8;14;18) with an MYC-IGH-BCL2 rearrangement resulting from translocation of BCL2 and MYC with a single disrupted IGH allele. Molecular cytogenetic investigation is essential to identify cases of high-grade leukaemia/lymphoma with concurrent translocations affecting the BCL2 and MYC loci.

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Section: Discussionmentioning

confidence: 99%

Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas

et al. 2005

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“…Pericentromeric rearrangements of Chr1 and Chr16 are overrepresented in diverse types of cancers, including hepatocellular carcinomas and Wilms tumors, and generally lead to gains of 1q and/or losses of 16q (Brito-Babapulle and Atkin, 1981;Le Baccon et al, 2001;Mitelman et al, 2001). In a study of hepatocellular carcinomas by comparative genomic hybridization, 23 out of the 36 tumors examined showed 1q gain; 22 of these displayed Chr1 Sat2 hypomethylation at BstBI sites (Wong et al, 2001).…”

Section: Hypomethylation Of Single-copy Genes In Cancermentioning

confidence: 99%

DNA methylation in cancer: too much, but also too little

2002

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Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but these two types of epigenetic abnormalities usually seem to affect different DNA sequences. Much more of the genome is generally subject to undermethylation rather than overmethylation. Genomic hypermethylation in cancer has been observed most often in CpG islands in gene regions. In contrast, very frequent hypomethylation is seen in both highly and moderately repeated DNA sequences in cancer, including heterochromatic DNA repeats, dispersed retrotransposons, and endogenous retroviral elements. Also, unique sequences, including transcription control sequences, are often subject to cancer-associated undermethylation. The high frequency of cancer-linked DNA hypomethylation, the nature of the affected sequences, and the absence of associations with DNA hypermethylation are consistent with an independent role for DNA undermethylation in cancer formation or tumor progression. Increased karyotypic instability and activation of tumor-promoting genes by cis or trans effects, that might include altered heterochromatin-euchromatin interactions, may be important consequences of DNA hypomethylation which favor oncogenesis. The relationship of DNA hypomethylation to tumorigenesis is important to be considered in the light of cancer therapies involving decreasing DNA methylation. Inducing DNA hypomethylation may have short-term anticancer effects, but might also help speed tumor progression from cancer cells surviving the DNA demethylation chemotherapy.

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“…β-catenin nuclear translocation has been identified as a key event that disturbs Wnt/β-catenin signaling and BCL-9, an extremely essential coactivator of the β-catenin-TCF complex and a novel therapeutic target (24,25). Our results show that, the ectopic expression of PCDH10 can hinder the protein expression of β-catenin and restrain its nuclear translocation as well as the expression of BCL-9.…”

Section: Discussionmentioning

confidence: 60%

“…Of note, the human BCL-9 gene, which was first identified by cloning the t(1;14)(q21;q32) translocation from a patient with B-cell acute lymphoblastic leukemia, has been identified as a critical coactivator of β-catenin activation in association with LEF/TCF family members. It has been confirmed that BCL-9 possesses a potent transcription activation domain, which is crucial for BCL-9 to promote β-catenin translocation and aberrant transcription of Wnt target genes, which in turn promotes tumor cell proliferation, disease progression and drug resistance (23)(24)(25). Those findings emphasize the importance of this pathway and BCL-9 for identification of appropriate target drugs.…”

Section: Introductionmentioning

confidence: 87%

PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway

Zhou

Yuan

et al. 2015

Oncology Reports

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Abstract. The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.

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Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B‐cell lymphoma and multiple myeloma

Cited by 88 publications

References 62 publications

Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas

Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas

DNA methylation in cancer: too much, but also too little

PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway

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