Table 1.
Clinical and mutational profiles of sequenced cases
| Case | Sex/age | BM diagnosis, FAB classification | BM cytogenetics | Presentation | Involved sites | Mean target coverage | Known somatic mutations (VAF) | Novel non-synonymous variants of unknown significance (VAF) |
|---|---|---|---|---|---|---|---|---|
| 1 | F/50 | AML with MDS-related change | 45,XX,del(5)(q?22q33),-7[13]/46,XX[7] | Isolated relapse | Left and right breasts, right ventricle, left axilla, both flank, inguinal area, and stomach antrum | 1447.59 | GNAQ_c.286A>T_p.T96S (5.7) IDH2_c.419G>A_p.R140Q (43.9) NRAS_c.35G>A_p.G12D (44.1) | |
| 2 | F/41 | AML M2 | 46,XX,t(8;21)(q22;q22) [10] | Isolated relapse | Right frontal lobe, scalp, both ovaries, neck LNs, bones, mesentery | 45.91 | SKT11_c.1190C>T_p.A397V (22) | ARID1A_c.757C>G_p.P253A (29) BRAF_start_gained (13.1) NOTCH1_c.1843G>A_p.G615R (21.8) |
| 3 | F/34 | AML M5a | 46,XX,t(11;19)(q23;p13.1)[17]/46,XX[3] | Isolated relapse | Rt. anterior chest, cervical and mediastinal LNs | 473.41 | NRAS_c.182A>T_p.Q61L (34.1) | NOTCH1_c.3350A>G_p.Q1117R (50) |
| 4 | F/47 | AML M2 | NK, FLT3+/NPM1+ | Isolated relapse | Rt. anterior chest skin, Rt. axilla, Lt. scapula, skull base, leptomeningeal seeding | 1506.30 | FLT3_c.1800_1801insTAGTATAAGTATAAGAGACTT_p.599D_600LinsDFREYEYD (77.9) IDH2_c.419G>A_p.R140Q (44.9) NPM1_ c.860_861insTCTG_ p.286L_287Wfs (37.6) | KDR_splice_site (15.8) PTCH2_ c.2668T>C_ p.Y890H (49.6) |
| 5 | M/22 | AML M5a | 47,XY,+8[3]/46,XY[4] | Isolated relapse | Skin | 1253.65 | KRAS_c.38G>A_p.G13D (48.7) PTEN_deletion (0, -1.99) | AURKB_c.487C>G_p.L163V (49.9) MTOR_ c.1919A>G_ p.H640R (64) 0NF1_c.7774C>A_p.H2592N (46.2) |
| 6 | M/70 | AML transformed from CMMoL | NK, no point mutations | Concurrent | Anterior chest | 152.40 | ERBB2_c.3149C>T_p.S1050L (39.4) NRAS_c.181C>A_p.Q61K (52.6) | BRCA1_c.4792T>C_p.S1598P (49.4) BRCA2_c.1342C>A_p.R448S (5.9) KDR_splice_site (19) NF1_c.668G>T_p.W223L (7) PDGFRA_c.2518G>A_p.A840T (16.9) |
| 7 | F/49 | AML M2 | 46,XX,t(8;21)(q22;q22)[20] | Concurrent | Right breast, cardiophrenic and retrosternal LNs, paravertebral TLS | 33.66 | KIT_c.2447A>T_p.D816V (60) | ATM_c.533C>T_p.P178L (21.4) BRCA2_c.6376T>C_p.C2126R (63.8) CSF1R_c.263G>C_p.G88A (45.2) JAK3_splice_site (61.1) |
| 8 | F/33 | AML M4 | NK, no point mutations | Concurrent | Nasopharynx | 1231.71 | GNAQ_c.286A>T_p.T96S (5.9) | ATRX_c.1492A>G_p.R498G (47.1) |
| 9 | F/60 | AML unclassified | 46,XX,16qh+[20], NPM1+ | Concurrent | Cervical and portocaval LNs, bones | 512.87 | IDH2_c.419G>A_p.R140Q (29.4) NPM1_ c.860_861insTCTG_ p.286L_287Trpfs (28.8) NRAS_c.37G>C_p.G13R (21.9) | APC_c.1984C>A_p.L662I (47.1) BRAF_start_gained (43.9) ROS1_splice_site (47.6) |
| 10 | F/60 | AML unclassified | 46,XX,t(6;9)(p22;q34), FLT3ITD+ | Concurrent | Left lower leg (skin), subcutaneous and intramuscular nodules, bones, lungs | 1183.80 | FLT3_c.1800_1801insTAGTATAAGTATAAGAGACTT_p.599D_600LinsDFRQYQYD (22.2) | FGFR1_splice_site (52.9) FLT3_ c.773C>T_p.P258L (50.1) |
| 11 | M/47 | AML M4 | 45,X-Y,t(8;21)(q22;q22),9qh-[20] | Marrow relapse | Left anterior chest wall | 231.44 | KIT_c.2447A>T_p.D816V (65.8) | APC_c.2651C>T_p.A884V (66) BRCA2_c.6715G>A_p.E2239K (47.8) BRCA2_c.7096C>G_p.L2366V (49.8) RB1_c.2035A>G_p.I679V (49.5) ROS1_c.6763T>C_p.S2255P (40.4) ROS1_c.6764C>T_p.S2255L (40.2) SMO_c.1068G>T_p.K356N (23.5) |
| 12 | M/60 | AML unclassified | 46,XY,t(1;7)(q21;p22)[3]/46,sl,t(4;21)(q21;q22)[3]/49,sdl1,+3,+8,+21[9]/46,XY[6] | Marrow relapse | Left humerus (pathologic fracture) | 553.88 | JAK2_c.1849G>T_p.V617F (72.4) | |
| 13 | M/11 | AML M4 | 46,XY,t(8;15)(q22;q26),inv(9)(p11q13),del(9)(q22)[10] | Concurrent | Gingiva, scrotum (sequential) | 124.07 | APC_c.904C>T_p.R302* (55) FBXW7_c.1634A>G_p.Y545C (95.9) KRAS_c.35G>A_p.G12N (43.5) PIK3CA_c.1634A>C_p.Q545A (38.2) RET_c.2053G>A_p.V685I (46.9) TP53_c.856G>A_p.E286K (70.3) | ALK_c.4433T>C_p.M1478T (5.1) APC_c.4461_4462delT_p.1486T_1487Lfs (50.6) NOTCH1_splice_site (7.7) SMO_c.1769G>C_p.S590T (31.4) |
BM bone marrow, AML acute myeloid leukemia, FAB French-American-British, VAF variant allele frequency, MDS myelodysplastic syndrome, LN lymph node, NK normal karyotype, CMMoL chronic monomyelocytic leukemia