Leukaemia Section Short Communication

Atlas Genet Cytogenet Oncol Haematol. 2013; 17(8) 568

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Atlas of Genetics and Cytogenetics in Oncology and Haematology

t(8;12)(q24;p12) LRMP/MYC Rashmi R Singh, Susana Ben-Neriah, Nathalie N Johnson, Joseph M Connors, Randy D Gascoyne, Douglas E Horsman

Center for Lymphoid Cancer, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6 Canada (RRS, SBN, NNJ, JMC, RDG, DEH)

Published in Atlas Database: March 2013

Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0812q24p12ID1618.html DOI: 10.4267/2042/51146

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2013 Atlas of Genetics and Cytogenetics in Oncology and Haematology

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

Disease Double-hit lymphoma

Phenotype/cell stem 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.

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.Clinics and pathology

t(8;12)(q24;p12) LRMP/MYC Singh RR, et al.

Atlas Genet Cytogenet Oncol Haematol. 2013; 17(8) 569

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.).

Genetics 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.

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 MYC (v-myc myelocytomatosis viral oncogene homolog (avian)) Location 8q24.21

DNA/RNA Transcription: alternative splicing; coding sequences: 1318 and 1362 bp for proteins p64 and p67 respectively.

Protein 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.

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 Size: 87334 bases. 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.

t(8;12)(q24;p12) LRMP/MYC Singh RR, et al.

Atlas Genet Cytogenet Oncol Haematol. 2013; 17(8) 570

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

Protein Size: 555 amino acids; 62122 Da.

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

References Tedoldi S, Paterson JC, Cordell J, Tan SY, Jones M, Manek S, Dei Tos AP, Roberton H, Masir N, Natkunam Y, Pileri SA, Facchetti F, Hansmann ML, Mason DY, Marafioti

T. Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas. J Pathol. 2006 Aug;209(4):454-63

Bertrand P, Bastard C, Maingonnat C, Jardin F, Maisonneuve C, Courel MN, Ruminy P, Picquenot JM, Tilly H. Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas. Leukemia. 2007 Mar;21(3):515-23

Singh RR, Ben-Neriah S, Johnson NN, Connors JM, Gascoyne RD, Horsman DE. 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. Leuk Res. 2012 Jan;36(1):e22-4

This article should be referenced as such:

Singh RR, Ben-Neriah S, Johnson NN, Connors JM, Gascoyne RD, Horsman DE. t(8;12)(q24;p12) LRMP/MYC. Atlas Genet Cytogenet Oncol Haematol. 2013; 17(8):568-570.