Table 1.
Chromosomal rearrangements detected in high-risk B-lineage ALL.
| Sample ID | Cohort | Rearrangement | Sex | Age (yr) | WCC × 109L | Key lesions | Karyotype |
|---|---|---|---|---|---|---|---|
| PAKTAL | P9906 | STRN3-JAK2* | Female | 12.2 | 478 | IKZF1 deletion and p.Leu117fs mutation | N/A |
| PAKKCA | P9906 | EBF1-PDGFRB* | Male | 11.7 | 236.4 | IKZF1 (IK6); EBF1 deletion; PAX5 inversion*; CDKN2A/CDKN2B deletion | 46, XY, del(6)(q13q23), del(9) (p22)[20] |
| PAKVKK | P9906 | NUP214-ABL1* | Male | 14.4 | 220.7 | IKZF1 p.Ser402fs mutation; PAX5 deletion; CDKN2A/CDKN2B deletion | N/A |
| PALIBN | P9906 | IGH@-EPOR* | Male | 14.3 | 29.9 | IKZF1 e1–5 deletion; CDKN2A/CDKN2B deletion | N/A |
| PAKYEP | P9906 | BCR-JAK2* | Male | 2.7 | 958.8 | IKZF1 (IK6); EBF1 deletion; PAX5 deletion and p.Gly24Arg mutation; CDKN2A/CDKN2B deletion | 47, XY,+2, del(2)(p23), t(3;22;9) (p12; q11.2; p24) [10]/46, XY[2] |
| PAMDRM | P9906 | IGH@-CRLF2** | Male | 7.9 | 351.3 | JAK2 p.Ile682_Arg683insGlyPro*; IKZF1 deletion e1-e6; EBF1 deletion; PAX5 p.Val319fs; CDKN2A/CDKN2B deletion | 46, XY[20] |
| PAKKXB | P9906 | IGH@-CRLF2** | Female | 14.5 | 92.7 | IKZF1 (IK6); CDKN2A/CDKN2B deletion; FLT3 p.Asn609ins23aa*** | 46, XX[21] |
| PALETF | P9906 | None | Female | 7.6 | 105.7 | EBF1 deletion; FLT3 p.Leu604ins23aa*** | 47, XX,+10[3]/46, XX,+10,−21[7]/46, XX[8] |
| PAKHZT | P9906 | IGH@-CRLF2** | Male | 13.9 | 307 | JAK2 p.Arg867Gln; CDKN2A/CDKN2B deletion | N/A |
| PALJDL | P9906 | None | Male | 3.2 | 156 | PAX5 deletion; CDKN2A/CDKN2B deletion; IL7R p.L242_L243insFPGVC mutation#; SH2B3 e1–2 deletion# | N/A |
| PANNGL | AALL0232 | PAX5-JAK2* | Female | 12.9 | 15.8 | IKZF1 deletion | 47, XX, r(7)(p12q31),+9[14]/46, XX[6] |
| PANSFD | AALL0232 | ETV6-ABL1* | Male | 5.4 | 83 | IKZF1 (IK6); PAX5 deletion; CDKN2A/CDKN2B deletion | 46, XY, ins(12;9)(p13; q34q34)[20] |
| PANEHF | AALL0232 | RCSD1-ABL1* | Male | 15.7 | 47.8 | N/A | N/A |
| SJBALL085 | Total XV | NUP214-ABL1* | Male | 16.3 | 135.6 | IKZF1 (IK6) and p.Ala79fs mutation* | 46, XY |
| SJBALL010 | Total XVI | RANBP2-ABL1* | Male | 15 | 121 | PAX5 deletion* | 46, XY, t(2;9)(q21; q34)[14]/46, XY[6] |
Chromosomal rearrangements affecting kinase and cytokine receptor signaling identified by mRNA-seq in 15 Ph-like cases. Genetic lesions disrupting B-cell development (IKZF1, EBF1, and PAX5) and JAK2 activating mutations are also shown. IK6 refers to the deletion of IKZF1 exons 4–7 (coding exons 3–6) that results in the expression of a dominant negative IKZF1 isoform that lacks the N-terminal DNA-binding zinc fingers. All cases were of B-precursor immunophenotype and did not exhibit expression of T-lineage markers. Frame shifts (fs) are designated using the short nomenclature as outlined by the Human Genome Variation Society. aa, amino acid; e, exon; ITD, internal tandem duplication; N/A, not available; WCC, white cell count (x109/L).
identified by RNA-seq analysis.
Previously known (Harvey et al., 2010a);
Previously known (Zhang et al., 2011);
Identified by whole genome sequencing. See Tables S1–S9.