TABLE 1.
Standard genetic testing pathway results compared to Optical Genome Mapping in ALL patients
| WHO classification | Karyotype FISH/RT‐PCR | Recurrent deletions detected by MLPA a | OGM formulab | Recurrent deletions detected by OGM a | Recurrent SVs and ploidy detected by OGM | |
|---|---|---|---|---|---|---|
| 1 | B‐ALL with TCF3::PBX1 |
46,XX,der(19)t(1;19)(q23;p13)[5]/46,XX[5] PBX1 and TCF3 rearranged |
ND |
ogm[GRCh37] 1q23.3q44(164940579_248630818)x3,t(1;19)(q23;p13.3)(164775625;1617441),ins(1;19)(q23;p13.3p13.3)(164775625;1617441_1759114inv),19p13.3(pter_1617442)x1 |
None | TCF3::PBX1 |
| 2 | B‐ALL NOS |
46,XX[20] No abnormalities detected by FISH |
None |
ogm[GRCh37] t(12;22)(p13.31;q13.2)(6795009;41525645) |
EP300 ::ZNF384 | |
| 3 | B‐ALL with ETV6::RUNX1 |
46,XY,del(6)(q16q24),add(11)(q23),?add(12)(p?),add(12)(q23),add(21)(q21),inc[11]/46,XY[2] Metaphase FISH complex t(11;12;21) ETV6::RUNX1 rearrangement |
Exon 2–6 PAX5, exon 8 ETV6 |
ogm[GRCh37] 6q15q23.2(90570707_132994084)×1,9p13.2p13.2(36924868_37031738)×1,t(11;12;21)(q24.2;p13;q22.11)(124542267;12034841;36326359),12p13.2p12.1(12034841_2497337)×1,21q21.1q22.12(16755788_36235050)×3 |
Exon 2–6 PAX5, exon 6–8 ETV6 |
ETV6::RUNX1 |
| 4 | B‐ALL with ETV6::RUNX1 |
46,XX[20] ETV6::RUNX1 rearrangement |
Exon 1–8 PAX5 |
ogm[GRCh37] Xq24q28(118659748_155008232)×3,t(X;21)(q24;q22.3)(118596968;48117142),9p13.2(36853610_37382413)×1,t(12;21)(p13.2;q22.12)(12034841;36420383) |
Exon 1–8 PAX5 |
ETV6::RUNX1 |
| 6 | B‐ALL NOS |
46,XX,del(3)(p13p26),der(9)t(3;9)(p13;p13)[6]/46,XX[1] No abnormalities detected by FISH |
Exon 7–10 PAX5, biallelic CDKN2A/2B |
ogm[GRCh38] t(3;9)(p13;p13.2)(71063635;36957140),9p24.3p13.2(14566_36957140)×1, 9p21.3(21825731_22009703)×0 |
Exon 7–10 PAX5, biallelic CDKN2A/2B |
PAX5::FOXP1 |
| 7 | B‐ALL with hyperdiploidy |
56,XX,+X,+4,+6,+8,+10,+14,+14,+17,+21,+21[2]/57,sl,+11[5]/46,XX[4] FISH compatible with hyperdiploid clone |
Exon 8 ETV6 |
ogm[GRCh38] (X)×3,(4)×3,(6)×3,(8)×3,(10)×3,(11)×3,12p13.2(11870531_119814480)×1,(14)×4,(17)×3,(21)×4 | Exon 6–8 ETV6 | |
| 8 | B‐ALL, BCR::ABL1‐like |
46,XX,t(8:9)(p22;p24)[1]/46,sl,der(8;9)(q10;q10),inc[6]/46,X,t(X;4)(p11;q1?3)[4]/46,XX[11] PCM1 and JAK2 rearranged |
ND | ogm[GRCh38] t(8;9)(p22;p24.1)(18021361;5060274),t(8;9)(q12.2;p24.1)(60671418;5961314),9p24.1p22.3(7306311_16265816)×1,9p21.3p21.2(21951394_27261605)×0,25 | PCM1::JAK2 | |
| 9 | B‐ALL NOS |
46,XX,del(9)(q22q33),der(19)t(1;19)(q23;p13)[6]/46,sl,del(13)(q13q21)[3]/46,XX[1] No TCF3::PBX1 rearrangement detected by FISH |
None | ogm[GRCh37] 1q21.2q44(149529883_249237532)×3,t(1;19)(q21.1;q13.43)(144837767;59111086),9q21.11q22.33(70321158_101956617)×1,19q13.43(59128983_qter)×1 | None | |
| 10 | B‐ALL with ETV6::RUNX1 |
46,XX,‐8,der(12)t(8;12)(q13;p13),+21[7]/46,XX[3] ETV6::RUNX1 rearrangement |
Exon 1–6 PAX5, ETV6 |
ogm[GRCh38] 8p23.3p11.23(61805_38264830)×1,t(8;12)(p11.23;p12.1)(38274465;26217459),9p13.2(36955993_372945461),12p13.33p12.1(14568_26225920)×1,t(12;21)(p13.2;q22.12)(11881907;35043931),(21)×3 |
Exon 1–6 PAX5, ETV6 |
ETV6::RUNX1 |
| 12 | B‐ALL with low hypodiploidy |
46,XX[20] FISH compatible with low hypodiploid clone |
None |
ogm[GRCh38] (X)×3,(1)×3,(5)×3,(6)×3,(8)×3,(10)×3,(11)×3,(14)×3,(15)×3,(18)×3,(19)×3,(21)×3,(22)×3 After manual correction of the ploidy:36,XX,–2,–3,–4,–7,–9,–12,dup(12p12.1p11.21)(22140659_31024594),–13,–16,–17,–20 |
None | After manual correction of ploidy: low hypodiploid clone |
| 13 | B‐ALL NOS |
45,X,‐Y[4]/46,XY,i(9)(q10),inc[3]/46,XY[16] No abnormalities detected by FISH |
None | ogm[GRCh38] t(1;19)(q23.3;p13.3)(164684214;1617442) |
None |
TCF3::PBX1 |
| 14 | B‐ALL NOS |
48,XY,+X,del(1)(q25q44),add(5)(q32),?der(7),+21[6]/46,XY[4] Trisomy X and 21 |
Exon 5–7 IKZF1, CDKN2A/2B |
ogm[GRCh37] (X)×2,t(1;5)(q22;q32)(156445725;149451946),5q35.2q35.3(175705336_180899715)×1,7p12.2(50451066_50467354)×1,9p21.3(21897504_22003647)×1,9p21.3(21975985_22019207)×1,17q24.3q25.3(70828023_77521027)×1,19q13.31q13.33(45144628_51391878)×1,(21)×3 |
Exon 5–7 IKZF1, CDKN2A/2B |
MEF2D::CSF1R |
| 15 | B‐ALL with BCR::ABL1 |
46,XX,t(9;22)(q34;q11)[2]/46,XX[6] BCR::ABL1 rearrangement |
Exon 4–8 IKZF1, downstream BTG1 | ogm[GRCh37] 7p12.2(50389810_51209685)×1,t(9;22)(q34.12;q11.23)(133647045;23548004),12q21.33(91794497_92538906)×1,t(13;22)(q14.11;q11.22)(41019582;22364735),19p13.12p12(16140309_21286406)×1,19q13.31q13.41(45026283_51442852)×1 | Exon 4–8 IKZF1, downstream BTG1 |
BCR::ABL1 IGL::FOXO1 |
| 16 | B‐ALL with low hypodiploidy |
32,XX,‐2,‐3,‐4,‐6,‐7,‐8,‐11,‐12,‐13,‐14,‐15,‐16,‐17,‐19[2]/37‐46,XX,inc[3] No structural or numerical abnormalities detected by FISH |
None | ogm[GRCh37] (X)×3,(1)×3,(5)×3,(9)×3,(10)×3,(11)×3,(18)×3,(19)×3,(21)×3,(22)×3 | None |
Manual correction of ploidy impossible due to low blast count: hyperdiploid clone |
| 17 | B‐ALL with iAMP21 |
47,XX,+X,add(3)(p21),del(4)(q?),del(12)(p11p13),add(14)(p11),‐21,+mar,inc[2]/45,sl,‐X,del(7)(p11p21)[2],add(10)(p11)[2],add(10)(p12),‐del(12),+add(12)(p11),‐mar[cp4]/46,XX[6] RUNX1 amplification by FISH |
ETV6, biallelic exon 19–26 RB1 | ogm[GRCh37] inv(2)(q33.1q35)(202530525;218107974),t(3;8)(p26.3;q21.2)(61829;84698449),4q21.22q26(82562646_118148833)×1,t(4;10)(q35.1;p12.2)(183938118;24572275),8q21.2q24.3(84747232_146301511)×3,10p15.3p12.2(64453_24569782)×4,10p12.2p11.21(24572275_35188421)×3,12p13.33p12.1(62597_32082761)×1,13q14.2(48981801_49089572)×0,14q11.2q32.33(20412883_106295617)×2,93,(21)cth,21q22.1q22.2(32113440_41074917)×8,25 |
ETV6, biallelic exon 18–27 RB1 gene |
Amplification RUNX1 |
| 18 | B‐ALL with hyperdiploidy |
55,XX,+4,+6,+8,+10,+14,+17,+18,+21,+21[4]/46,XX[6] FISH compatible with hyperdiploid clone |
None | ogm[GRCh38] (4)×3,(6)×3,(8)×3,(10)×3,(14)×3,(17)×3,(18)×3,(21)×4 | None | High hyperdiploid clone |
| 27 | B‐ALL NOS |
46,XY[23] No abnormalities detected by FISH |
None | ogm[GRCh38] inv(9)(p24.1p13.2)(5081915;36992699) | None | PAX5::JAK2 |
| 29 | B‐ALL with ETV6::RUNX1 |
46,XX[20] ETV6::RUNX1 rearrangement |
Exon 2–6 PAX5, ETV6 | ogm[GRCh38] 9p13.2(36924871_37031741)×1,10p15.3p11.23(2148472_29605241)×3, t(10;12)(p11.23;p12.3)(29628820;15233701),12p13.33p12.3(14568_15233701)×1,t(12;21)(p13.2;q22.12)(11870531;35029693) |
Exon 2–6 PAX5, ETV6 |
ETV6::RUNX1 |
| 30 | B‐ALL with BCR::ABL1 |
46,XX,t(9;22)(q34;q11)[8]/46,sl,add(16)(p12)[2] BCR::ABL1 rearrangement |
Exon 4–7 IKZF1, CDKN2A/2B, PAX5, exon 19–26 RB1, exon 2 BTG1 + downstream |
ogm[GRCh38] t(1;16)(q21.1;p13.3)(143361930;14134),7p12.2(50324505_50399656)×1,t(9;22)(q34.12;q11.23)(130709559;23244051),9p21.3(21925732_22165462)×1,9p13.2(36759965_37121784)×1,12q21.33(91882647_92145130)×1,13q14.2(48402465_48510295)×1 |
Exon 3–7 IKZ1,CDKN2A/2B, PAX5,exon 18–27 RB1, exon 2 BTG1 + downstream |
BCR::ABL1 |
| 31 | B‐ALL NOS |
46,XX,idic(9)(p1?3)[7]/46,XX[3] No abnormalities detected by FISH |
CDKN2A/2B, PAX5 | ogm[GRCh38] 9p24.3p12(14566_39591818)×1,9p12q34.3(39788526_136344539)×3 | CDKN2A/2B, PAX5 | |
| 32 | B‐ALL with hyperdiploidy |
56,XX,+X,+4,+6,+8,+10,+17,+18,+21,+21,+mar[7]/55,sl,t(15;15)(q21;q24),‐17[2]/46,XX[2] FISH compatible with hyperdiploid clone, unbalanced rearrangement of IGH |
CDKN2A/2B, exon 1 ETV6 | ogm[GRCh38] (X)×3,(4)×3,(6)×3,(8)×3,9p21.3(21636919_23285480)×1,(10)×3, 12p13.2(11635931_11654206)×1,(14)×3,t(14;14)(q11.2;q32.33)(22422983;106294644),(17)×3,(18)×3,(21)×4 |
CDKN2A/2B, exon 1 ETV6 |
TRA::IGH |
| 34 | B‐ALL NOS |
91<4n>,XXYY,‐17,idic(17)(p11)[8]/92<4n>,XXYY[1]/46,XY[5] FISH compatible with tetraploid clone |
Not informative (low blast count) | ogm[GRCh38] ins(9;?)(p13.2;?)(9:37012419_37031741ins(?:?_?),17p13.3p11.2(1315080_16299764)×1,78 | TP53 |
PAX5::ZNF318 Tetraploidy not detected |
| 35 | B‐ALL with hyperdiploidy |
55,XY,+X,+4,+6,+8,+11,+14,add(17)(p13),+18,+21,+21,inc[7]/46,XY[7] FISH compatible with hyperdiploid clone |
CDKN2A/2B | ogm[GRCh38] (X)×2,(4)×3,(6)×3,(8)×3,9p21.3(20360830_23290064)×1,(11)×3,(14)×3,t(17;17)(p13.3;q21.2)(320531;42625238)17q21.2q25.3(42621068_83246392)×3,(18)×3,(21)×4 |
CDKN2A/2B |
High hyperdiploid clone |
| 36 | B‐ALL NOS |
46,XY,‐2,?t(9;17)(p13;q21),del(11)(q21q23),?der(14)t(2;14)(?p11;q32),+mar[8]/46,XY[1] Loss of entire KMT2A gene by FISH |
None | ogm[GRCh38] t(9;17)(p13.2;q22.12)(37205108;48932814),10p15.3p11.22(18514_31936573)×3,t(10;11)(p11.22;q22.1)(32029500;100293717),11q22.1q25(100233393_135069565)×1 | KMT2A | |
| 37 | B‐ALL with hyperdiploidy |
60,XY,‐5[5],+6,+8,+10,+11[5],+12,+14[5],+15,+16[5],+17,+18[3],+21,+21[5],+3‐7mar,inc[cp6]/46,XY[3] FISH compatible with hyperdiploid clone |
CDKN2A/2B, deletion of exon 2 ETV6 (only 2 copies) | ogm[GRCh38] (X)×2,(4)×3,(5)×3,t(4;5)(q34.3;q31.1)(179501025;136258772),t(5;5)(q33.1;q35.3)(152558057;187110343),t(5;10)(q33.2;q23.31)(153843504;90199407),t(5;10)(q35.1;q24.2)(171252456;97709101),9p21.3(21801680_22314347)×1,(6)×3,(8)×3,(10)×4,(12)×3,12p13.2(11699080_11790985)×1,(14)×3,(16)×3,(17)×3,(18)×3,(21)×4 |
CDKN2A/2B, exon 2 ETV6 |
High hyperdiploid clone |
| 38 | B‐ALL, BCR::ABL1‐like |
46,XX[20] IGH::CRLF2 rearrangement |
IKZF1, exon 1–2 ETV6, exon 2 + downstream BTG1 |
ogm[GRCh38] 3p21.31p12.2(44984632_81647686)×1,7p14.1p12.1(36363239_50695470)×1,12p13.2 (11635931_11818565)×1,12q21.33(91882647_92145130)×1,17p13.3p11.2(66653_19154549)×1,17q11.1q25.3(26692353_79373278)×3 | IKZF1, exon 1–2 ETV6, exon 2 + downstream BTG1 | Software version 1.6 or higher: t(X;14)(p22.33;q32) IGH::CRLF2 |
| 39 | B‐ALL NOS |
46,XX,+8,‐20[1]/46,sl,der(9)t(9;20)(p13;p11)[16]/46,XX[9] No abnormalities detected by FISH |
Biallelic CDKN2A/2B, exon 10 PAX5 |
ogm[GRCh38] (8)×3,9p24.3p13.2(14566_37056711)×1,(9)(p21.3)(21897505_22009703)×0,t(9;20)(p13.2; q11.21)(36866463;32456682),20q11.21q13.33(32456682_64333718)×1 | Biallelic CDKN2A/2B, exon 9–10 PAX5 | PAX5::ASLX1 |
| 40 | B‐ALL NOS |
47,XX,+21[9]/47,sl,add(3),add(6),‐12,add(14),+mar[1]/47,sl,add(3) (q13),del(4)(q13q24),add(6)(p11),‐12,add(14)(p11),+mar[2]/46,XX[8] Trisomy 21 |
None | ogm[GRCh38] (21)×3 | None | |
| 41 | B‐ALL with TCF3::PBX1 |
46,XX,del(6)(q16q25),der(19)t(1;19)(q23;p13)[10] TCF3::PBX1 rearrangement |
None |
ogm[GRCh38] 1q23.3q44(164679641_248943333)×3,t(1;19)(q23.3;p13.3)(164694931;1617442),6q14.1q22.1(77866354_115226336)×1,19p13.3(pter_1617442)×1 |
None |
TCF3::PBX1 |
| 5 | T‐ALL |
46,XY[15] No abnormalities detected by FISH |
ogm[GRCh38] t(1;14)(p33;q32)(47227936;106586104),14q32(106586104_106607463)×1 |
IG H::TAL1 |
||
| 11 | T‐ALL |
46,XY[11] TRB::HOXA10 |
ogm[GRCh37] inv(7)(p15.2q34)(27231194;142508528) |
TRB::HOXA10 | ||
| 19 | T‐ALL |
46,XY,t(11;14)(p13;q11)[3]/46,XY[12] FISH TRD::LMO2 rearrangement/RT‐PCR: STIL::TAL1 rearrangement |
ogm[GRCh38] 1p33(47227936_47325742)×1,t(11;14)(p13;q11.2)(33816961;22082444) |
STIL::TAL1 TRD::LMO2 |
||
| 20 | T‐ALL |
46,XY[1] Suspected rearrangement of TRA/D by FISH |
ogm[GRCh38] t(5;11)(q31.1;p11.2)(134127916;47361335) |
TCF7::SPI1 | ||
| 21 | T‐ALL |
46,XY[27] No abnormalities detected by FISH |
ogm[GRCh38] 9p21.3p21.2(21082754_26785046)×0,38,t(14;14)(q11.2;q13.3 )(22442014;36521900) | TRA::NKX2‐1 | ||
| 22 | T‐ALL |
46,XY,del(6)(q15q23),t(7;11)(q34;p13),add(16)(p12)[11]/46,sl,del(8)(q12q21)[2]/46,XY[2] TRB::LMO2 rearrangement by FISH |
ogm[GRCh38] t(4;10)(q35.2;q26.3)(190058514;133630087),6q11.1q21(62507864_110148938)×1,t(7;11)(q34;p13)(142810844;33848837) |
TRB::LMO2 t(4;10) DUX4::FRG2B False positive (not confirmed by FISH) |
||
| 23 | T‐ALL |
46,XY,?del(10)(q23q25)[6]/46,XY[17] No abnormalities detected by FISH/RT‐PCR STIL::TAL1 |
ogm[GRCh38] 1p33(47227936_47324493)×1 |
STIL::TAL1 |
||
| 24 | T‐ALL |
46,XY[15] TLX3 rearrangement by FISH |
ogm[GRCh38] t(5;14)(q35.1;q32.2)(171333079;98622030),13q12.2q21.31(27781122_63486427)×1 |
?BCL11B::TLX3 |
||
| 25 | T‐ALL |
46,XY,add(6)(q22),add(14)(q2?4)[16]/46,XY[1] No abnormalities detected by FISH |
ogm[GRCh38] t(6;6)(q24.2;q25.3)(144332634;157040528) or inv(6)(q24.2q25.3),t(6;14)(q24.2;q32.2)(144332634;99277645),t(6;14)(q25.3;q32.2)(156271735;99266630) |
BCL11B::? |
||
| 26 | T‐ALL |
46,XX[20] TRA/D rearrangement by FISH |
ogm[GRCh38] t(2;14)(q22.3;q11.2)(144622655;22496144) | TRA::ZEB2 | ||
| 28 | T‐ALL |
46,XY[16] TRB rearrangement by FISH |
ogm[GRCh38] t(7;7)(p15.2;q34)(27549839;142784716),7q34q36.3(142784716_159334984)×1,12p12.2p12.1(20367120_26146317)×1 | TRB::HIBADH | ||
| 42 | T‐ALL |
46,XY,add(4)(q21),add(7)(q34),idic(9)(p13),der(9;9)(p10;p10),inc[2]/46,XY[8] TRB rearrangement by FISH |
ogm[GRCh37] 4p16.3p15.1(12985_29399657)×1,inv(4)(p15.1p13)(29414444;43347003),t(7;10)(q34;q24.31)(142508527;102897948),inv(8)(p21.3p11.21)(19781043;41512623),9p24.3p13.1(14566_38792295)×1,9p21.3(21535833_24382513)×0,9q21.11q34.2(70321158_137096384)×3 | TRB::TLX1 | ||
Note: Bold refined breakpoints, resolving cytogenetic findings and identification of additional clinically relevant SVs.
Abbreviations: ALL, acute lymphoblastic leukemia, MLPA, multiple ligation dependent probe amplification, ND, not determined, OGM, optical genome mapping, SV, structural variant.
If no exons are mentioned, the entire gene is deleted.
OGM formula abnormalities adapted according to guidelines.