Genomic technologies for detecting structural variations in hematologic malignancies

Mi‑Ae Jang

doi:10.1007/s44313-024-00001-1

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Blood Res (2024) 59:1

Published online February 13, 2024

https://doi.org/10.1007/s44313-024-00001-1

Genomic technologies for detecting structural variations in hematologic malignancies

Mi‑Ae Jang^1*

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¹ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon‑Ro, Gangnam‑Gu, Seoul 06351, Korea

Correspondence to : * Mi‑Ae Jang
miaeyaho@gmail.com

Received: December 5, 2023; Accepted: December 18, 2023

Abstract

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Abstract

Genomic structural variations in myeloid, lymphoid, and plasma cell neoplasms can provide key diagnostic, prognostic, and therapeutic information while elucidating the underlying disease biology. Several molecular diagnostic approaches play a central role in evaluating hematological malignancies. Traditional cytogenetic diagnostic assays, such as chromosome banding and fluorescence in situ hybridization, are essential components of the current diagnostic workup that guide clinical care for most hematologic malignancies. However, each assay has inherent limitations, including limited resolution for detecting small structural variations and low coverage, and can only detect alterations in the target regions. Recently, the rapid expansion and increasing availability of novel and comprehensive genomic technologies have led to their use in clinical laboratories for clinical management and translational research. This review aims to describe the clinical relevance of structural variations in hematologic malignancies and introduce genomic technologies that may facilitate personalized tumor characterization and treatment.

Keywords Molecular diagnostics, Next-generation sequencing, Leukemia, Lymphoma, Myeloma, Myeloid, Lymphoid

Article

REVIEW

Blood Res 2024; 59():

Published online February 13, 2024 https://doi.org/10.1007/s44313-024-00001-1

Genomic technologies for detecting structural variations in hematologic malignancies

Mi‑Ae Jang^1*

¹ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon‑Ro, Gangnam‑Gu, Seoul 06351, Korea

Correspondence to:* Mi‑Ae Jang
miaeyaho@gmail.com

Received: December 5, 2023; Accepted: December 18, 2023

Abstract

Keywords: Molecular diagnostics, Next-generation sequencing, Leukemia, Lymphoma, Myeloma, Myeloid, Lymphoid

Abstract

Table 1 . Key somatic structural variations of diagnostic and/or prognostic values in selected hematologic malignancies.

Disease subtype	Prognostic implication	Chromosomal/molecular abnormality
Myeloid neoplasms AML [11]	Good. Intermediate. Poor.	t(8;21)(q22;q22.1), inv(16)(p13.1q22) or t(16;16)(p13.1;q22). t(9;11)(p21.3;q23.3). t(6;9)(p23;q34.1), t(v;11q23.3), t(9;22)(q34.1;q11.2), inv(3)(q21.3q26.2) or t(3;3)(q21.3q26.2), -5 or del(5q), -7, -17/abn(17p), complex karyotype, monosomal karyotype.
MDS [16]	Very good. Good. Intermediate. Poor. Very poor.	-Y, del(11q). normal karyotype, del(5q), del(12p), del(20q), double including. del(5q) del(7q), + 8, + 19, i(17q), any other single or double independent clones. -7, inv(3)/t(3q)/del(3q), double including -7/del(7q), complex: 3 abnormalities. complex karyotype > 3 abnormalities.
CML [17]	Poor	+ 8, + Ph, i(17q), + 19, -7/7q-, 11q23 or 3q26.2 aberrations, complex karyotype
Lymphoid neoplasms B-ALL [10]	Good. Poor.	t(12;21)(p13;q22), high hyperdiploidy (51–65 chromosomes). t(9;22)(q34.1;q11.2), hypodiploidy (≤ 45 chromosomes), iAMP 21, t(17;19)(q22;p13), t(v;11q23.3).
CLL [18]	Favorable. Intermediate. Unfavorable.	del(13q) (as a sole abnormality). normal karyotype, + 12. del(17p), del(11q).
MM [19]	High risk	del(17p), t(4;14)(p16;q32), t(14;16)(q32;q23)
FL [20]		t(14;18)(q32;q21)
MCL [20]		t(11;14)(q13;q32)
Burkitt [20]		t(8;14)(q24;q32)

Abbreviations: AML acute myeloid leukemia, MDS myelodysplastic syndrome, CML chronic myeloid leukemia, B-ALL B-lymphoblastic leukemia/lymphoma, CLL chronic lymphocytic leukemia, MM multiple myeloma, FL follicular lymphoma, MCL mantle cell lymphoma, + Ph second or extra copy of the Ph chromosome, iAMP21 intrachromosomal amplification of chromosome 21.

Table 2 . Comparative characteristics of available genomic technologies for hematologic malignancies.

Method	CBA	FISH	CMA	RT-PCR	Targeted sequencing		WGS	WTS	OGM
Analyte	Living cells	DNA in interphase and metaphase	DNA	RNA	DNA	RNA	DNA	RNA	DNA
Coverage	Genome-wide	Targeted	Genome-wide	Targeted	Targeted	Targeted	Genome-wide	Genome-wide	Genome-wide
Individual cell clone identification	Yes	Yes	No	No	No	No	No	No	No
Ability to multiplex	Low	Low	High	High	High	High	High	High	Low to medium
Resolution	> 5–10 Mb	> 100 Kb	> 15 Kb	NA	Single base	Single base	Single base	Single base	0.5–5 kb (for SV), 500 kb (for CNV)
Detection range
SVs	Yes	Yes	No	Limited	Limited	Yes	Yes	Yes	Yes
CNVs	Yes	Yes	Yes	Limited	Limited	Limited	Yes	Limited	Yes
SNVs	No	No	No	No	Yes	Yes	Yes	Yes	No

Abbreviations: CBA chromosome banding analysis, FISH fluorescence in situ hybridization, CMA chromosomal microarray, RT-PCR reverse transcriptase PCR, WGS whole genome sequencing, WTS whole transcriptome sequencing, OGM optical genomic mapping, NA not available, SV structural variation, CNV copy number variation, SNV single-nucleotide variant.