DNA‐methylation analysis identifies the E‐cadherin gene as a potential marker of disease progression in patients with monoclonal gammopathies

S, Seidl; Ackermann, Jutta; Kaufmann, H.; Keck, Andrea; Nösslinger, Thomas; Zielinski, Christoph; Drach, Johannes; Zöchbauer‐Müller, Sabine

doi:10.1002/cncr.20295

Cited by 66 publications

(66 citation statements)

References 38 publications

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“…The serial determinations reported here therefore suggest that IgH translocations as well as del(13q) do not immediately precede the transition from stable MGUS to progressive MM. We rather hypothesize that presence of such chromosomal aberrations in MGUS plasma cells may facilitate the emergence of other molecular events (eg ras mutations and dysregulation of other oncogenes, 2,3 epigenetic changes, 21 genes implicated in various signaling pathways 22 ) that eventually lead to progression to MM. Prospective follow-up of individuals with MGUS will be required to resolve the issue of whether or not time to progression from MGUS to MM may be different depending on the primary chromosomal event(s).…”

Section: Serial Fish Studies Of Mgus and Myeloma H Kaufmann Et Almentioning

confidence: 97%

Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma

et al. 2004

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Molecular and genetic events associated with the transition from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are still poorly characterized. We investigated serial bone marrow specimens from 11 patients with MGUS who eventually progressed to MM (MM post-MGUS) by interphase fluorescence in situ hybridization for immunoglobulin heavy-chain gene (IgH) translocations and chromosome 13q deletions (del(13q)). In nine patients, IgH translocations were present both in MGUS and MM post-MGUS plasma cells, including three t(11;14)(q13;q32) and one t(4;14)(p16;q32), which was observed already 92 months prior to MM. Similarly, all five MM patients with del(13q) had this aberration already at the MGUS stage. Two patients without IgH translocation and del(13q) had chromosomal gains suggesting hyperdiploidy, but IgH translocations and/or del(13q) did not emerge at MM post-MGUS. IgH translocations and del(13q) are early genetic events in monoclonal gammopathies, suggesting that additional events are required for the transition from stable MGUS to progressive MM.

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Section: Serial Fish Studies Of Mgus and Myeloma H Kaufmann Et Almentioning

confidence: 97%

Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma

et al. 2004

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“…The majority of these genes have known relevance to myeloma biology, such as CDKN2C and RB1 (cellcycle regulation), TRAF3, BIRC2, BIRC3 and CYLD (NF-B regulation), [6][7][8] WWOX (apoptosis), 7,32 GSK3A (Wnt signaling), 14,33 and CDH1 (frequently methylated). 34,35 Pathways analysis of deregulated genes in myeloma…”

Section: Impact Of Homozygous Deletionsmentioning

confidence: 99%

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value

Walker

Leone

Chiecchio

et al. 2010

Blood

327

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To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-B pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111. (Blood. 2010;116(15): e56-e65)

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“…73 Finally, in a larger study on 142 patients with MM or MGUS, P73 methylation was detected in 15 and 21% of them, respectively. 74 Thus, silencing of P73 gene by its methylation is markedly associated also with MG.…”

Section: P73 Gene Hypermethylationmentioning

confidence: 99%

The role of p73 in hematological malignancies

et al. 2006

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The P73 gene is a homologue of the P53 tumor suppressor. Owing to its structural similarity with p53, p73 was originally considered to have tumor suppressor function. However, the discovery of N-terminal truncated isoforms with oncogenic properties showed a 'two in one' structure of its product, p73 protein. The full-length variants are strong inducers of apoptosis, whereas the truncated isoforms inhibit proapoptotic activity of p53 and the full-length p73. Thus, p73 is involved in the regulation of cell cycle, cell death and development. Moreover, it plays a role in carcinogenesis and controls tumor sensitivity to treatment. p73 is commonly expressed in tumor cells in hematological malignancies. Overexpression of p73 protein and aberrant expression of its particular isoforms, with very low frequency of P73 hypermethylation or mutations, were found in malignant myeloproliferations, including acute myeloblastic leukemia. In contrast, hypermethylation and subsequent inactivation of the P73 gene are the most common findings in malignant lymphoproliferative disorders, especially acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphomas. Assessment of P73 methylation may provide important prognostic information, as was confirmed in patients with ALL. This review summarizes some aspects of p73 biology with particular reference to its possible pathogenetic role and prognostic significance in hematological malignancies.

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DNA‐methylation analysis identifies the E‐cadherin gene as a potential marker of disease progression in patients with monoclonal gammopathies

Cited by 66 publications

References 38 publications

Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma

Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value

The role of p73 in hematological malignancies

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