Table 1.

Clinical implementation of high-throughput sequencing.

Platform	Capability	Cost	Detectable Subtypes	Difficult Subtypes
WTS (RNAseq)	Fusion chimeras Gene expression profiling Mutant allele expression Alternative splicing analysis (BCR/TCR rearrangements) (Sequence mutations) (Copy number analysis)	Moderate	B-ALL ETV6-RUNX1; KMT2A; TCF3-PBX1; BCR-ABL1; DUX4; MEF2D; ZNF384/362 NUTM1; HLF; BCL2/MYC; PAX5alt; ZEB2/CEBPE; -like subtypes	B-ALL Aneuploidies
			T-ALL HOXA (KMT2A-R, PICALM-MLLT10, SET-NUP214); SPI1; NKX2-1; TAL1 (STIL-TAL1)	T-ALL BCL11B; TLX1/3; LMO1/2; HOXA (others); TAL1 (others); T-other
WGS	Sequence mutations Structural variants Copy number analysis (BCR/TCR rearrangements) (GWAS)	High	B-ALL Aneuploidies; ETV6-RUNX1; KMT2A; TCF3-PBX1; BCR-ABL1; DUX4; MEF2D; ZNF384/362; NUTM1; HLF; BCL2/MYC; PAX5 P80R; IKZF1 N159Y; ZEB2/CEBPE; Sequence and structural alterations in Ph-like ALL	B-ALL -like subtypes; Part of PAX5alt
			T-ALL BCL11B; TLX1/3; LMO1/2; HOXA; SPI1; NKX2-1; TAL1	T-ALL T-other
WES	Sequence mutations (coding) Structural variants (coding) Copy number analysis	Moderate	B-ALL (Aneuploidies) PAX5 P80R IKZF1 N159Y Sequence mutations in Ph-like ALL (e.g., JAK1/2/3, Ras)	Most of other B-ALL and T-ALL subtypes
Targeted sequencing (DNA and/or RNA)	Fusion chimeras (targeted) Gene expression (targeted) Sequence mutations (targeted) Structural variants (targeted) (Copy number analysis)	Low	Targeted alterations	Non-targeted alterations

The parenthesis in “Capability” indicates analyses in development. Abbreviations: WTS: whole transcriptome sequencing; BCR: B-cell receptor; TCR: T-cell receptor; WGS: whole genome sequencing; GWAS: genome wide association study; WES: whole exome sequencing; -R: rearranged.