Letter to the Editor
Ann Lab Med 2021; 41(3): 342-345
Published online May 1, 2021 https://doi.org/10.3343/alm.2021.41.3.342
Copyright © Korean Society for Laboratory Medicine.
LSAMP Rearrangement in Acute Myeloid Leukemia With a Jumping Translocation Involving 3q13.31
1Department of Laboratory Medicine, Korea University Guro Hospital, Seoul, Korea; 2Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Korea; 4Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to: Sun-Hee Kim, M.D., Ph.D.
Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-2704, Fax: +82-2-3410-2719, E-mail: firstname.lastname@example.org
Jumping translocations (JTs) are rare but recurrent cytogenetic abnormalities in hematological malignancies and solid tumors . Of the JTs reported in hematological malignancies, those involving chromosome 3q are the second most frequently observed donor segment [2-4]. However, to date, the impact of JTs involving 3q13.3 on the pathogenesis of leukemia has not been elucidated . We describe the first RNA-sequencing (RNA-seq) data of a
The patient was a 72-year-old man who was referred for a bone marrow (BM) study at Samsung Medical Center in April 2018 owing to the observation of 30% blasts on a peripheral blood smear. The BM study revealed 66% of blast cells with monocytoid differentiation. The patient was diagnosed as having AML, not otherwise specified, subtype acute monocytic leukemia. The patient was treated with decitabine for induction therapy due to his age; however, he died during the re-induction therapy owing to leukostasis and tumor lysis syndrome.
Conventional karyotyping was performed as previously described , and fluorescence
RNA was extracted from a BM aspirate using the RevertAid First Strand cDNA Synthesis Kit (Thermo Fisher Scientific, Waltham, MA, USA). Paired-end libraries were prepared using the TruSeq RNA Sample Prep Kit (V2; Illumina, San Diego, CA, USA) and sequenced using a HiSeq 2500 instrument (Illumina). The sequence reads were mapped using STAR (version 2.4.0; https:// github.com/alexdobin/STAR) and quantified using RSEM (version 1.3.1; https://github.com/deweylab/RSEM). RSEM was also applied to generate the normalized gene expression in terms of transcripts per million values and to quantify the isoform-level expression of
Conventional cytogenetic analysis of the BM aspirate demonstrated three related cytogenetically aberrant clones (Fig. 1). The jumping donor chromosome bands ranging from 3q13.3 to qter translocated to three recipient chromosome regions: 12q24.3, 13p13, and 18p11.3. The G-banding karyotypic results were: 47,XY,+8,der(18)t(3;18)(q13.3;p11.3)/47,XY,+8,der(12) t(3;12)(q13.3;q24.3)/47,XY,+8,der(13)t(3;13)(q13.3;p13) /46,XY. FISH analysis using RPN1/MECOM, a dual color dual fusion probe, detected 24.0% of cells (48/200) with three MECOM signals on 3q26.2.
Figure 1. G-banding karyotype. Closed arrows indicate the JT breakpoints at each derivative chromosome. Karyotype showing (A) trisomy 8 and der(12)t(3;12)(q13.3;q24.3), (B) trisomy 8 and der(13)t(3;13)(q13.3;p13), and (C) trisomy 8 and der(18) t(3;18)(q13.3;p11.3). (D) Partial karyotype showing the JT in-volving 3q13.3.
Abbreviation: JT, jumping translocation.
The chromosomal microarray showed partial trisomy of 3q13. 32-q29 (genomic position 117,967,114–197,851,986) and a single copy gain of 8p23.3-8q24.3 (genomic position 158,048– 146,295,771), which likely indicates trisomy 8. Moreover, a 385kb submicroscopic interstitial deletion at 3q13.31 (genomic position 116,234,782–116,620,270) was observed.
RNA-seq was performed to analyze the structural changes formed via the JT. A breakpoint resulting in a fusion between
Figure 2. The fusion transcript of the JT involving 3q13.3 identified by RNA-sequencing analysis and Sanger sequencing. (A) Chromosomal array demonstrating the breakpoints corresponding to an interstitial deletion of 3q13.31 and a gain in 3q13.32-q29. (B) Partial sequences surrounding
LSAMPand the intergenic region fusion showing the junction of LSAMPexon 1 and the intergenic region (chr3:117,716,029). (C) Schematic diagrams of genomic breakpoints mapped with blue and red arrows indicating each breakpoint. The thick blue boxes represent the coding exon and 5´ untranslated region. The thin red line represents the DNA introns and intergenic regions.
Abbreviation: JT, jumping translocation.
Gene expression was compared with the RNA expression data of 3q13.3 JT-negative AML patients. AML with a JT involving 3q13.3 showed significantly higher expression of
JT-caused truncation or loss of the gene located near the donor chromosome breakpoint has been observed .
Kim SH contributed to the conception and design of the study; Kim HY, Jang HY, Kim HJ, and Kim SH were involved in clinical evaluation; Cho EH and Kim HY interpreted the results; Yun JW performed the statistical analysis; Yoon J drafted the manuscript; and Kim SH supervised the study. All authors read and approved the final manuscript.
CONFLICTS OF INTEREST
No potential conflicts of interest relevant to this study are reported.
- Berger R and Bernard OA. Jumping translocations. Genes Chromosomes Cancer 2007;46:717-23.
- Kjeldsen E. Characterization of an acquired jumping translocation involving 3q13.31-qter in a patient with de novo acute monocytic leukemia. Exp Mol Pathol 2017;103:14-25.
- Bernard M, Lemée F, Picard F, Ghandour C, Drenou B, Le Prise PY, et al. Jumping translocation in acute leukemia of myelomonocytic lineage: a case report and review of the literature. Leukemia 2000;14:119-22.
- Reis MD, Dubé ID, Pinkerton PH, Chen-Lai J, Robinson JB, Klock RJ, et al. "Jumping" translocations involving band 3q13.3 in a case of acute monocytic leukemia. Cancer Genet Cytogenet 1991;51:189-94.
- Shin SY, Lee ST, Kim HJ, Cho EH, Kim JW, Park S, et al. Mutation profiling of 19 candidate genes in acute myeloid leukemia suggests significance of
DNMT3Amutations. Oncotarget 2016;23:54825-37.
- Hatakeyama S, Osawa M, Omine M, Ishikawa F. JTB: a novel membrane protein gene at 1q21 rearranged in a jumping translocation. Oncogene 1999;18:2085-90.
- Chen J, Lui WO, Vos MD, Clark GJ, Takahashi M, Schoumans J, et al. The t(1;3) breakpoint-spanning genes
LSAMPand NORE1are involved in clear cell renal cell carcinomas. Cancer Cell 2003;4:405-13.
- Ntougkos E, Rush R, Scott D, Frankenberg T, Gabra H, Smyth JF, et al. The IgLON family in epithelial ovarian cancer: expression profiles and clinicopathologic correlates. Clin Cancer Res 2005;11:5764-8.
- Yen CC, Chen WM, Chen TH, Chen WY, Chen PC, Chiou HJ, et al. Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving
LSAMPgene in osteosarcoma. Int J Oncol 2009;35:775-88.
- Petrovics G, Li H, Stümpel T, Tan SH, Young D, Katta S, et al. A novel genomic alteration of
LSAMPassociates with aggressive prostate cancer in African American men. EBioMedicine 2015;2:1957-64.