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

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Bibliography

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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)

External Links