t(8;12)(q24;p12) LRMP/MYC

2013-03-01 Susana Ben-Neriah , Nathalie N Johnson , Joseph M Connors , Randy D Gascoyne , Douglas E Horsman , Rashmi R Singh Affiliation

1.Center for Lymphoid Cancer, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6 Canada

Clinics and Pathology

Disease

Double-hit lymphoma

Phenotype stem cell origin

B-cell lymphoma.

Epidemiology

Rare translocation first described in a B-cell lymphoma cell line by Tedoldi et al. 2006.

Clinics

Unknown.

Prognosis

Unknown.

Note

In the study by Tedoldi et al., Jaw1/LRMP was found in three-quarters (24/32) of the diffuse large B-cell lymphoma (DLBCL) cases classified phenotypically as being of germinal centre type and also expressed in almost half (13/28) of the non-germinal centre cases.

Cytogenetics

Cytogenetics morphological

The conventional karyotype analysis revealed 47,X,add(X)(p22), del(1)(p36.3), t(8;12)(q24;p12.1),+der(12)t(8;12), t(14;18)(q32;q21) [7]/46, XX [1].

Cytogenetics molecular

A. Fosmid dual color break apart probes spanning the LRMP gene on 12p12 shows a similar break apart pattern as commercial MYC probe.
B. Molecular fusion of the fosmid probes spanning the LRMP gene observed with MYC on 8q24.
C. FISH analysis for mapping translocation breakpoints on MYC revealed a mono allelic deletion of the BAC clone RP11-125A17 (PVT1 locus) with 1Y1R pattern in 100% of metaphase and interphase cells analyzed.

A. FISH image depicts fosmid dual color break apart probe created by the combination of G248P87899B1 (WI2-3266N3) (labeled in green) and G248P89329G2 (WI2-1668D2) (labeled in red) from 12p12.1 shows a similar break apart signal pattern as MYC dual color breakapart probe (shown above) in a metaphase and interphase cells. B. FISH image depicts fusion of fosmid probes G248P87899B1/G248P89329G2 (labeled in red) spanning the LRMP gene on 12p12.1 with "in house" MYC probe (RP11-440N18/RP11-125A17) (labeled in green) on 8q24. C. FISH analysis using "in-house" BAC probes for mapping breakpoints on MYC [RP11-440N18 (Sp. R.) and RP11-125A17 (Sp.G.)] revealed mono allelic deletion of RP11-125A17 (Sp. G.).

Probes

G248P87899B1 (WI2-3266N3) (labeled in green) and G248P89329G2 (WI2-1668D2) (labeled in red) for LRMP gene on chromosomal locus 12p12.1 and RP11-440N18 and RP11-125A17 for MYC gene on 8q24. Probes provided by Dr Wan Lam, BC Cancer Agency.

Variants

Not known.

Genes Involved and Proteins

Gene name

MYC v-myc myelocytomatosis viral oncogene homolog (avian)

Location

8q24.21

Dna rna description

Transcription: alternative splicing; coding sequences: 1318 and 1362 bp for proteins p64 and p67 respectively. , Location base pair of fosmids used for the breakpoint analysis of the gene:
, G248P89329G2 starts at 25155029 and ends at 25191825,
, G248P87899FB1 starts at 25237532 and ends at 25280488.

Location base pair starts at 128748315 and ends at 128753680 bp from pter (according to hg19-Feb_2009).

Protein description

439 amino acids and 48 kDa in the p64; 454 amino acids in the p67 (15 additional amino acids in N-term to C-term: a transactivation domain, an acidic domain, a nuclear localization signal, a basic domain, an helix-loop-helix motif, and a leucine zipper; DNA binding protein.

Gene name

LRMP (lymphoid restricted membrane protein)

Location

12p12.1

Note

Other name Jaw1.
This is the first known chromosomal translocation in a B-cell lymphoma involving LRMP gene with MYC on 8q24.

Dna rna description

Size: 87334 bases.

Protein description

Size: 555 amino acids; 62122 Da.

Result of the Chromosomal Anomaly

Description

Fusion of LRMP/Jaw1 observed with MYC on 8q24. Refer to Figure B (see above in the section of image molecular).

Bibliography

Pubmed ID	Last Year	Title	Authors
17230227	2007	Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas.	Bertrand P et al
21996557	2012	Identification of a novel non-immunoglobulin/MYC translocation t(8;12)(q24;p12) involving the LRMP gene in a primary B-cell lymphoma. A case report.	Singh RR et al
16739114	2006	Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas.	Tedoldi S et al

Summary

Fusion gene

LRMP/MYC LRMP (12p12.1) MYC (8q24.21) M t(8;12)(q24;p12)

Note

This is a novel translocation in a single case involving chromosomal band 12p12 and MYC on 8q24.

The G-banding karyotype analysis of this case revealed t(8;12)(q24;?p11),+der(12)t(8;12) in addition to the t(14;18)(q32;q24). Further, metaphase FISH analysis (Left) using the commercial MYC dual color break apart probe revealed a fused yellow signal on chromosome 8 indicating a normal copy, a red signal on derivative 8 and two derivative 12 chromosomes carrying the telomeric portion of MYC labeled in Spectrum Green. The Interphase cells (Right) also revealed a 1F1R2G pattern in 100% of the cells that were scored.

Citation

Susana Ben-Neriah ; Nathalie N Johnson ; Joseph M Connors ; Randy D Gascoyne ; Douglas E Horsman ; Rashmi R Singh

t(8;12)(q24;p12) LRMP/MYC

Atlas Genet Cytogenet Oncol Haematol. 2013-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1618/t(8;12)(q24;p12)