Table 1
List of diseases and genes covered in the next generation sequencing analysis.
| Disease | Genes Covered |
|---|---|
| Acute lymphoblastic leukemia (ALL) | ASXL2, ATM, BRAF, CALR, CDKN2A, CREBBP, CRLF2, CSF3R, CTCF, DNM2, EGFR, EP300, FBXW7, GATA2, HNRNPK, HRAS, IKZF3, IL7R, KDM6A, KDR, KMT2C, LRRC4, MAP2K1, MLH1, MSH2, MSH6, NOTCH1 NTRK3, PAX5, PDGFRA, PMS2, PRAMEF2, PTEN, RELN, SMARCB1 |
| Acute myeloid leukemia (AML) | ANKRD26, ASXL1, ATM, BCOR, BCORL1, BIRC3, BRAF, C17orf97, CALR, CARD11, CBLC, CDKN2A, CEBPA, CHEK2, CREBBP, CSF1R, CSF3R, CTCF, DAXX, DDX41, DNM2, DNMT1, ELANE, EP300, FLRT2, FLT3, GATA1, GATA2, HNRNPK, IDH1, IDH2, IKZF1, IL7R, JAK1, JAK3, KDM6A, KDR, KIT (CD117), KMT2A, KMT2C, KRAS, LRRC4, MAP2K1, MPL, MSH6, MYC, NBN, NOTCH1, NPM1, NRAS, NSD1, NTRK3, OR13H1, OR8B12, P2RY2, PCDHB1, PDGFRA, PHF6, PRAMEF2, PRPF8, PTEN, PTPN11, RAD21, RUNX1 (AML1), SF1, SF3A1, SMARCB1, SMC1A (SMC1L1), SMC3, SRP72, SRSF2, STAG2, STXBP2, U2AF1, U2AF2, WT1 |
| Chronic lymphocytic leukemia (CLL) | ADA, BIRC3, BLM, BRAF, CALR, CHEK2, CSF3R, KCNA4, KLHL6, KMT2C, MAP2K1, NBN, NPAT, NTRK3, OR13H1, OR8B12, PRAMEF2, SRP72, TAL1, TERT, TUBA3C, WAS, WRN |
| Chronic myeloid leukemia (CML) | ABL1, CALR, CDKN2A, CEBPA, CREBBP, CSF1R, CSF3R, FBXW7, GATA2, KDM6A, MSH2, MSH6, RB1, SMC1A (SMC1L1), TP53 |
| Chronic myelomonocytic leukemia (CMML) | CALR, CEBPA, CSF1R, CSF3R, HRAS, KMT2C, LUC7L2, SRSF2 |
| Chronic neutrophilic leukemia (CNL) | CALR, CSF3R |
| Multiple myeloma (MM) | ATM, BCL6, BCR, BIRC3, BRAF, CDKN2A, CEBPA, EGFR, FBXW7, GJB3, HRAS, KDM6A, MYC, NOTCH1, PTEN, SH2D1A, SMARCB1 |
| Myelodysplastic syndromes (MDS) | ATRX, CALR, CDKN2A, CEBPA, CSF1R, CSF3R, EP300, ETNK1, GNAS, HRAS, KDM6A, KMT2A, KMT2C, RAD21, RB1, SETBP1, SF1, SF3A1, SMC3, SRSF2, STAG2, U2AF1, U2AF2, XPO1, ZRSR2 |
Table 2
Frequencies of genetic abnormalities in patients who were evaluated with conventional cytogenetic/ fluorescent in situ hybridization and next generation sequencing.
| Cytogenetic Abnormalities | n (%) |
|---|---|
| No metaphase | 10 (28.00) |
| Normal karyotype | 25 (71.40) |
| FISH Abnormalities | |
| –13/del(13q) | 3 (8.57) |
| –17/del(17p) | 2 (5.71) |
| t(11;14)(q13;q32)/IgH-CCND1 | 2 (5.71) |
| t(4;14)(p16;q32)/IgH-FGFR3 | 2 (5.71) |
| t(14;16)(p32;q23)/IgH-MAF | – |
| Chromosome 1 amplification (CKS1B/CDKNC gene) | 4 (11.42) |
| NGS Results | |
| Pathogenic variations | 10 (28.57) |
| Likely pathogenic variations | 3 (8.57) |
| Variants of unknown significance (VUS) | 11 (31.42) |
Table 3
Comparison of next generation sequencing and fluorescent in situ hybridization/karyotype results.
| Sex-(years) Age | Pathogenic Variations | FISH Abnormalities | Cytogenetic Evaluation | |
|---|---|---|---|---|
| M-70 | NRAS: c.181C>A | normal | 46,XY | |
| F-74 | NRAS: c.183A>T | CDKN2C; CKS1B×3; IgH/FGFR3+ | – | |
| M-41 | normal | D13S25; 13qter; RB1×1; CKS1B×3; IgH/FGFR3+ | 46,XY | |
| F-67 | NRAS: c.181C>A | CKS1B; CCND1; P53; CEP17×3 | 46,XX | |
| M-58 | DNMT3A: c.2645G>A | normal | 46,XY | |
| M-74 | normal | CKS1B×4 | 46,XY | |
| M-61 | SFTP353B1: : c.c.8181866G>G>A T | VUS CBLB: c.1472A>G | RB1; D13S25×1 | 46,XY |
| M-68 | TNFRSF13B: c.310T>C | normal | – | |
| F-71 | TET2: c.3543_3544delCT | P53×1 | 46,XX | |
| M-69 | ATM: c.2250+2T>A | RB1; D13S25×1 | 46,XY | |
| F-67 | normal | CCND1×3; CKS1B×4 | – | |
| M-64 | ASXL1: c.1141G>T | likely FLT3: pathogenic c.2678C>T | normal | 46,XY |
| F-70 | KRAS: c.183A>C | normal | – | |
| F-76 | TERT: c.2035T>G | normal | – | |
| F-63 | VUS AKAP13: c.7265G>A | normal | – | |
| F-52 | MYD88: c.815G>A | normal | – | |
| F-66 | CBLB: c.2434G>A | normal | 46,XX | |
| F-67 | BLM: c.2237C>T | normal | 46,XX | |
| F-58 | CBLBCSF3: Rc.: c.1927355A>G>G A | normal | 46,XX | |
| F-49 | SF3A1: c.458T>C | normal | 46,XX | |
| M-84 | SF3B1: c.422A>G | normal | – | |
| M-50 | ASXL1: c.143G>T | normal | 46,XY | |
| F-72 | MPL: c.1481T>G | normal | 46,XX | |