Table 1.
Comparison of cytogenetic and genomic findings from nine patients with adverse-risk AML
| Case | Karyotypea | Complex karyotype | Composite karyotype | No. of cytogenetic abnormalities | CNVsb | Chromosomal rearrangementsb | Gene fusions | SNVs | |
|---|---|---|---|---|---|---|---|---|---|
| Total | NGS concordant | ||||||||
| 1 | 51, XY, +Y, +der(1;7)(q10;p10), +6, +8, +10 [10] | Yes | 5 | 5 | Gains: 1q, 6, 7p, 8, 10, Y | RUNX1, PTPN11, BCOR | |||
| 2 | 45, XX, -7 [17] / 45, X, t(X;8)(p21.2;q24.1), -7 [2] / 46, XX[1] | 2 | 2 | Losses: 7, BCOR | t(X;8)(p11.4;q24.13) linked to BCOR deletion; t(3;15)(p24.3;q14) | IDH2 | |||
| 3 | 43~45, X, -Y, t(1;5)(q21;p13), t(1;6)(q21;p25), -2, add(2)(p21), add(3)(q27), del(3)(q27), add(4)(p16), del(4)(q33), del(5)(q31), add(6)(p25), del(6)(q21), -7, add(7)(q36), del(7)(q22), -8, add(8)(q24.3), del(8)(?q23), +del(8)(q22), add(9)(p22), add(9)(q34), add(11)(p15), add(12)(p13), -16, add(16)(p13.3), -17, der(17)t(11;17)(q13;p13), add(18)(q23), der(19)t(11;19)(q13;q13.3), -21, add(22)(p11.2), +4mar [cp20] | Yes | Yes | 31 | 9 |
Gains: 1p36.33-p35.1, 2p25.3-p22.3, 2p21-p11.2 (BCL11A), 3q26.32-q29, 8q12.1-q23.1 (RUNX1T1), 11q13.4-q25 (ETS1), 12p13.33-p13.2, 17q25.1-q25.3 (SRSF2), 19p13.3, 20q13.32-q13.33 Losses: 2q11.2-q31.3, 7q21.3-q36.2, 11p15.5-p13 (WT1), 16q13-q24.3 (CTCF), 17p13.3-p12 (TP53), 17q11.2-q24.3 (NF1), 19q13.42-q13.43, Yq11.221-q12 |
t(1;5)(q42.3;q12.3); t(3;12) (q26.2;p13.2) linked to gene fusion; t(9;20)(q34.11;q13.12); der(Y)t(Y;3)(q11.221;q26.32) linked to 3q gain and Yq loss; chr4/7 rearrangements linked to 7q loss; chr2/3/8/11/12/16/17/ 19/22/X rearrangements linked to CNVs | ETV6-MECOM | TP53 |
| 4 | 48-49, XX, +6, +8, +9, t(12;17)(p13;q11.2), i(17)(q10), inv(18)(q11.2q21) [cp20] | Yes | Yes | 6 | 5 |
Gains: 6, 8, 9 Losses: 17p13.3-p13.1 (TP53), 18q21.2 (SMAD4) |
t(11;12;17)(p15.4;p13.3;q11.2) linked to gene fusion (Figure 1) | NUP98-KDM5A | ASXL1 |
| 5 | 46, XY, del(6)(q21q23), t(10;11)(p1?2;q21), inv(12)(q15q24.1), del(15)(q2?4) [cp19] / 46, XY [1] | Yes | Yes | 4 | 3 | Losses: ARPP21, BBX, 6q16.1-q22.31 (FOXO3), MACC1, 8p12-p11.21 (FGFR1), 8q11.21-q11.23, SH2B3, TBX3, MIR5009, SETD4 | t(10;11)(p12.3;q14.2) linked to gene fusion; t(7;18) linked to MACC1 del; chr12 rearrangements linked to SH2B3 and TBX3 deletions | PICALM-MLLT10; FIP1L1-PDGFRA (only in relapse) | |
| 6 | 46, XX, del(5)(q31), t(11;12)(p13;p13) [4] / 45, idem, -13 [5] / 46, XX [1] | Yes | 3 | 3 | Losses: FHIT, CDH18, 5q22.2q32 (APC), LACE1/FOXO3, 11p13 (WT1), 11p13-p12, 12p13.2-p12.3 (ETV6), 12p11.1, 12q12, 13, SLC47A1 | chr11/12/17 rearrangements linked to CNVs and gene fusion (Figure 1) | NUP98-BPTF | WT1, ETV6 | |
| 7 | 43~48, XY, +?Y, +?Y, der(5)t(5;17)(q1?3;q11.2), -7, +8, -12, -13, t(16;18)(q24;q23), +1~2mar [cp10] | Yes | Yes | 8 | 5 |
Gains: 8, 13q12.11-q12.2 (FLT3) Losses: 1p36.12-p36.11 (RPL11), 1p35.3-p35.2, 1p22.1-p21.3, 2p13.3-p13.1, 2p12-p11.2, 2q32.2-q37.3 (SF3B1), 5q11.2-q35.3 (APC, NPM1), 7, 12p13.2-p12.1 (ETV6), 12p12.1-p11.21, 12q12-q24.13, TCF12, 16q21-q22.2 (CTCF), 16q22.3-q24.3, 17p13.3-p11.2 (TP53), 17q11.2-q12 (NF1), 18p11.31, 18q22.3-q23 |
chr1 rearrangements linked to three segmental losses; chr2/5/8/12/13/16/17/18 rearrangements linked to other CNVs; inv(7)(q11.22q36.3) | TP53 | |
| 8 | 42-45, X, der(X)t(X;3)(q28;q21), der(1)t(1;17)(p35;q21), -3, -5, add(8)(q13), -9, add(11)(q13), add(12)(q24), i(13)(q10), del(16)(q23), -17, -18, -19, +idic(22)(p12), +2r, +mar1 [cp9] / 46, XX [1] | Yes | Yes | 14 | 6 |
Gains: 3q13.33-q29, 8q (MYC), 13, 22 Losses: 3, 5q31.1, 5q31.2-q35.3 (NPM1), SMARCA2, 9p13.2-p11.2 (PAX5), 9q33.1-q33.3, 12p13.33-p11.23 (ETV6), 16q21-q24.3 (CTCF), 17p13.2-p11.2 (TP53), 17q11.2-q12 (NF1), 19p13.2-p13.12 (JUNB), BCOR, KDM6A |
chr1/5/8/9/11/12/16/17/19 rearrangements linked to CNVs | TP53 | |
| 9 | 46, XX, t(1;14)(q21;q11.2) [20] | 1 | 1 | t(1;14)(q23.2;q12) linked to truncation of ATP1A2 | DNMT3A, FLT3, TET2 | ||||
a Bold font in karyotype denotes cytogenetic abnormalities that are exactly or closely matched by the NGS findings, which are enumerated in the “NGS concordant” column.
b Bold font in CNVs and chromosomal rearrangements denotes NGS findings that match or may explain the cytogenetic abnormalities. For CNVs, gains and losses are listed for chromosomes (i.e. 7), chromosome arms (i.e. 7p), subchromosomal segments (i.e. 12p13.2), and genes (i.e. BCOR). Key genes for large segments are shown in brackets when applicable.