t(8;9)(q24;p13) ?/MYC

2013-10-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)

Phenotype stem cell origin

There were 5 cases of ALL (L3-ALLs and CD10+ ALLs in 2 cases each), 11 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of unclassifiable B-cell lymphoma, one case of follicular lymphoma, and one case of diffuse mixed small and large cell lymphoma (Levine et al., 1989; Nacheva et al., 1993; Dunphy et al., 2003; DAchille et al., 2006; Bertrand et al., 2007; Le Gouill et al., 2007; Christie et al., 2008; Johnson et al., 2009; Subramaniyam et al., 2011).

Epidemiology

Twenty five cases are available. There were 12 male and 13 female patients, median age was 63 years (range 42-90 years). In a review of NHLs with a t(14;18)(q32;q21), the incidence of MYC translocations was 5%, and the incidence of t(8;9)(q24;p13) was 1% (Johansson et al., 1995).
Atlas Image
Meta-analysis of survival in patients with t(8;9)(q24;p13).

Prognosis

Median survival was 4 months (see figure). However, patients with an ALL died at 1, 1, 1.5, and 1.5 months. Median survival of patients with NHL was 6 months, and 3 out of 19 NHL patients were still alive 5 years after diagnosis (16%).

Genes Involved and Proteins

Note
Breakpoints occurred close to MYC on chromosome 8 and close to: ZBTB5, ZCCHC7, and PAX5 on chromosome 9 (Bertrand et al., 2007; Le Gouill et al., 2007; Johnson et al., 2009).
- ZBTB5 is a POZ domain Krüppel-like zinc finger transcription repressor. ZBTB5 interacted with co-repressor-histone deacetylase complexes such as BCOR, NCOR1, and NCOR2 (SMRT), resulting in deacetylation of histones Ac-H3 and Ac-H4, and transcriptional repression of CDKN1A (p21) (Koh et al., 2009).
- ZCCHC7 is the equivalent of the yeast AIR1. In yeast, a number of unwanted RNA transcripts are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. TRAMP facilitates pre-mRNA splicing (Kong et al., 2013).
- PAX5 is a lineage-specific transcription factor; recognizes the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is any nucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes and represses genes involved in other lineage commitments. Activates the surface cell receptor CD19 and represses FLT3. PAX5 physically interacts with the RAG1/RAG2 complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells are restored in their function in mature B cells and plasma cells, and PAX5 repressed (Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007).
Gene name
MYC v-myc myelocytomatosis viral oncogene homolog (avian)
Location
8q24.21
Protein description
DNA binding protein. Binds DNA as a heterodimer with MAX. Involved in various cellular processes including cell growth, proliferation, cell adhesion, apoptosis, angiogenesis, and stem cell behaviour modulation.

Result of the Chromosomal Anomaly

Expression localisation

There was abundant MYC expression in all the cases studied.

Highly cited references

Pubmed IDYearTitleCitations
374509232024MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.590
352033952022Normal and Neoplastic Growth Suppression by the Extended Myc Network.410
368356282023The "Superoncogene" Myc at the Crossroad between Metabolism and Gene Expression in Glioblastoma Multiforme.330
369021752023When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases.264
309094962019MYC Oncogene Contributions to Release of Cell Cycle Brakes.243
366118332022Lessons from Using Genetically Engineered Mouse Models of MYC-Induced Lymphoma.234
333222392020The Molecular 'Myc-anisms' Behind Myc-Driven Tumorigenesis and the Relevant Myc-Directed Therapeutics.230
224643212012MYC on the path to cancer.229
345082582022The MYC oncogene - the grand orchestrator of cancer growth and immune evasion.227
263821452015MYC, Metabolism, and Cancer.223
283982292017Controlling the Master: Chromatin Dynamics at the MYC Promoter Integrate Developmental Signaling.217
305979972018Therapeutic Inhibition of Myc in Cancer. Structural Bases and Computer-Aided Drug Discovery Approaches.212
349784692022Target c-Myc to treat pancreatic cancer.206
379419012023MYC function and regulation in physiological perspective.191
369690252023Strategies to target the cancer driver MYC in tumor cells.186
338015992021Gene Transactivation and Transrepression in MYC-Driven Cancers.181
383903242024Targeting MYC at the intersection between cancer metabolism and oncoimmunology.180
304513652019Intricate crosstalk between MYC and non-coding RNAs regulates hallmarks of cancer.174
389570162024Immune evasion: An imperative and consequence of MYC deregulation.164
264164272015MYC-driven aggressive B-cell lymphomas: biology, entity, differential diagnosis and clinical management.162
349424442022Therapeutic targeting of "undruggable" MYC.159
318325152019Writing and erasing MYC ubiquitination and SUMOylation.159
346588882021Targeting Myc Interacting Proteins as a Winding Path in Cancer Therapy.158
357414022022MTBP and MYC: A Dynamic Duo in Proliferation, Cancer, and Aging.156
282455972017MYC in Regulating Immunity: Metabolism and Beyond.142
252747552014Therapeutic strategies to inhibit MYC.138
364178492022MYC regulates a pan-cancer network of co-expressed oncogenic splicing factors.127
320714362020Target gene-independent functions of MYC oncoproteins.126
367346152023Demystifying the Druggability of the MYC Family of Oncogenes.122
336923312021Alternative approaches to target Myc for cancer treatment.121
341786662021Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy.120
374571232023Targeting MYC-driven lymphoma: lessons learned and future directions.116
321605432020MYC Dysregulates Mitosis, Revealing Cancer Vulnerabilities.105
383024732024Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.103
330920252020MYC in Brain Development and Cancer.99
295273312018Targeting oncogenic Myc as a strategy for cancer treatment.97
304703032018The MYC Enhancer-ome: Long-Range Transcriptional Regulation of MYC in Cancer.94
367650892023Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability.93
180329162007Feedback regulation of c-Myc by ribosomal protein L11.88
351153712022MYC overexpression leads to increased chromatin interactions at super-enhancers and MYC binding sites.86
385652492024A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.84
291730172020MYC leads the way.81
352447242022The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase.77
369306772023TXNIP loss expands Myc-dependent transcriptional programs by increasing Myc genomic binding.75
371059892023DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC.68
327159942020Dissecting transcriptional amplification by MYC.68
316798232019Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy.67
363519452022Reversible Myc hypomorphism identifies a key Myc-dependency in early cancer evolution.66
254757042015Taming of the beast: shaping Myc-dependent amplification.65
378527962023MYC acetylated lysine residues drive oncogenic cell transformation and regulate select genetic programs for cell adhesion-independent growth and survival.64
243949402014c-MYC-miRNA circuitry: a central regulator of aggressive B-cell malignancies.63
314551582019Oncogenic MYC amplifies mitotic perturbations.61
270814792016Strategically targeting MYC in cancer.59
349119362021Androgen receptor and MYC equilibration centralizes on developmental super-enhancer.59
332989112020TRIB3 promotes MYC-associated lymphoma development through suppression of UBE3B-mediated MYC degradation.55
352177902022Prostate-specific oncogene OTUD6A promotes prostatic tumorigenesis via deubiquitinating and stabilizing c-Myc.53
391220092024SOX2 represses c-MYC transcription by altering the co-activator landscape of the c-MYC super-enhancer and promoter regions.53
332753072021Gold-Based Pharmacophore Inhibits Intracellular MYC Protein.52
204452242010Cdk2: a key regulator of the senescence control function of Myc.52
324828682020MYC protein stability is negatively regulated by BRD4.50
352967952022Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis.50
279264802017Calcium-dependent binding of Myc to calmodulin.44
248571452014Taking on challenging targets: making MYC druggable.40
351676212022Cryptic MYC insertions in Burkitt lymphoma: New data and a review of the literature.39
329668062021Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC.37
385466912024MYC overexpression in natural killer cell lymphoma: prognostic and therapeutic implications.36
359621892022Myc inhibition tips the immune balance to promote antitumor immunity.36
382072062024MYC rearrangements in HIV-associated large B-cell lymphomas: EUROMYC, a European retrospective study.35
354380572022Ubiquitylation of unphosphorylated c-myc by novel E3 ligase SCF(Fbxl8).32
381847532024Non-IG::MYC in diffuse large B-cell lymphoma confers variable genomic configurations and MYC transactivation potential.26
263831672015The MYC-WDR5 Nexus and Cancer.24
335247942021MYC as a target for cancer treatment.0
247042062015Myc and cell cycle control.0
95584771998The many roles of c-Myc in apoptosis.0
17515431991c-myc oncoprotein function.0
88227951996Myc-mediated apoptosis.0
249331132015Myc and its interactors take shape.0
385838182024Exploring Myc puzzle: Insights into cancer, stem cell biology, and PPI networks.0
310680322019MYC modulators in cancer: a patent review.0
255642542015MYC-mediated synthetic lethality for treatment of hematological malignancies.0
255535142015MYC-mediated synthetic lethality for treating tumors.0
340192882021MYC Analysis in Cancer and Evolution.0
340192832021An "-omycs" Toolbox to Work with MYC.0
126283472003Transcriptional repression by Myc.0
291710172017Pathogenesis and therapeutic targeting of aberrant MYC expression in haematological cancers.0
320745952020The Spectrum of MYC Alterations in Diffuse Large B-Cell Lymphoma.0
30349331987Myc family of cellular oncogenes.0
246084282015Targeting RNA polymerase I to treat MYC-driven cancer.0
394682222025Transcriptional regulation by MYC: an emerging new model.0
236963622013Myc in stem cell behaviour: insights from Drosophila.0
247318542015The activities of MYC, MNT and the MAX-interactome in lymphocyte proliferation and oncogenesis.0
198060172009MYC, microRNAs and glutamine addiction in cancers.0
393066152024MYC upstream region orchestrates resistance to PI3K inhibitors in cancer cells through FOXO3a-mediated autophagic adaptation.0
116078122001Translocations involving c-myc and c-myc function.0
217042292011Proteolytic control of the oncoprotein transcription factor Myc.0
13633641992DNA binding by the Myc oncoproteins.0
207135262010Tipping the balance: Cdk2 enables Myc to suppress senescence.0
105799121999Function of the c-Myc oncogenic transcription factor.0
116844362001The interplay between Mad and Myc in proliferation and differentiation.0
125658162003Mechanisms of c-myc-mediated transcriptional repression of growth arrest genes.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
172302272007Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas.Bertrand P et al
182975232008C-MYC translocation in t(14;18) positive follicular lymphoma at presentation: An adverse prognostic indicator?Christie L et al
174404522007Pax5: the guardian of B cell identity and function.Cobaleda C et al
170745912006Translocation (14;18)(q32;q21) in acute lymphoblastic leukemia: a study of 12 cases and review of the literature.D'Achille P et al
127089082003Mature B-cell acute lymphoblastic leukemia with associated translocations (14;18)(q32;q21) and (8;9)(q24;p13). A Burkitt variant?Dunphy CH et al
150040082004Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.Fuxa M et al
75793601995Cytogenetic evolution patterns in non-Hodgkin's lymphoma.Johansson B et al
152585792004B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K et al
195971842009Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival.Johnson NA et al
194913982009A novel POK family transcription factor, ZBTB5, represses transcription of p21CIP1 gene.Koh DI et al
240974362014Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing.Kong KY et al
180243712007The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement.Le Gouill S et al
25069531989Four new recurring translocations in non-Hodgkin lymphoma.Levine EG et al
83242251993C-MYC translocations in de novo B-cell lineage acute leukemias with t(14;18)(cell lines Karpas 231 and 353).Nacheva E et al
217181392011De novo B lymphoblastic leukemia/lymphoma in an adult with t(14;18)(q32;q21) and c-MYC gene rearrangement involving 10p13.Subramaniyam S et al
166801442006Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.Zhang Z et al

Citation

Jean-Loup Huret

t(8;9)(q24;p13) ?/MYC

Atlas Genet Cytogenet Oncol Haematol. 2013-10-01

Online version: http://atlasgeneticsoncology.org/haematological/2141/t(8;9)(q24;p13)