Analysis of mutations in exon 2 of GATA1 in AML in DS patients
. | . | . | . | . | Exon 2 mutation (according to NM_002049) . | . | . | . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Patient . | Sex . | Age at diagnosis, mo . | DNA source (blasts in PB/BM, %) . | Karyotype . | RNA . | Last normal GATA1 amino acid . | Consequence of mutation on protein . | Clinical status at last follow-up (time since diagnosis, mo) . | ||
| 1 | F | 17 | PB (84) | 47,XX,+8,+21c[20] | 202delAG | Gly31 | Stop codon before Met84 | DOD (6) | ||
| 2 | M | 22 | PB (24) | 48,XY,del(6)(q21q24),+21,+21c[20] | 296ins19 | Ala61 | Stop codon before Met84 | DOD (4) | ||
| 3 | F | 21 | PB (68) | 47,XX,inv(9)(p11q13)c,+21c[1]/47,XX,idem,der(4)t(1;4) (q23;p15)[17]/47,XX,idem, iso(7)(q10)[2] | IVS2+2T>C | Pro73 | Splice mutant | CCR (77) | ||
| 4 | M | 23 | PB (51) | 47,XY,+21c[18]/48,XY,+8,+21c[1]/49,XY,+8,+12,+21c[1] | 262delG | Pro50 | Stop codon after Met84 | CCR (47) | ||
| 5† | M | 13 | PB (8) | 47,XY,t(2;4)(q37;q28),+21c[20] | 297insA | Ala61 | Stop codon before Met84 | CCR (67) | ||
| 6 | F | 23 | BM (24) | 47,XX,+21c[7]/47,XX,der(7)t(1;7)(q22;p22), +21c[11]/47,XX,dup(1)(q22q44), +21c[2] | 272ins10 | Ala53 | Stop codon before Met84 | CCR (75) | ||
| 7 | M | 23 | BM (41) | 47,XY,+21c[16]/48,XY,+8,+21c[4] | 263del43 | Pro50 | Stop codon after Met84 | CCR(66) | ||
| 8 | F | 15 | PB (98) | 47,XX,+21c[20] | 113A>G | Met1Val | No translation from Met1 | DOD (0)* | ||
| 9 | F | 35 | BM (17) | Not determined | 225C>T† | Pro38Leu | Polymorphism† | CCR (8) | ||
| 11B‡ | M | 11 | BM (20) | 47, XY +21 | 202delAG | Gly31 | Stop codon before Met84 | CCR (29) | ||
| 14 | F | 31 | BM (>20) | 48,XX,+8,+21c[9/25] | 332G>T | Pro73 | Splice mutant | CCR (95) | ||
| 21 | F | 31 | BM (38.5) | 48,XX,+8,+21c[7]/47,XX,+21c[2] | 292ins11 | Leu60 | Stop codon after Met84 | CCR (25) | ||
| 24 | F | 11 | BM (33) | 47,XX,+21c | 115G>A | Met1Ile | No translation from Met1 | CCR (67) | ||
| 25 | M | 44 | BM (55) | 48,XY,+21c,+mar1,+mar2[7]/49,X, -Y,+8,+11,+21c,+mar1[2] | 161C>T | Pro16 | Stop codon before Met84 | CCR (24) | ||
| 26 | F | 20 | BM (23) | 47,XX,+21c[4]/46,XX[2] | 301del11,ins22 | Tyr63 | Stop codon after Met84 | Died of sepsis in CCR (4) | ||
| 48 | M | 26 | BM (40) | 47,XY+21,-11,-13,+3mar | Normal | Ser413 | CCR (19) | |||
| 49† | M | 50 | BM (70) | Not determined | 116G>T | Met1 | Stop codon before Met84 | DOD (34) | ||
| 62B‡ | M | 22 | BM (40) | 41-45,del(X)(p22),Y,-4,add(5)(p15),-7[3],-8,-9[8],-11,-12[8],-15,del(17)(p11),+21c,+der(21)add(21)(p?)?,-22[7]+3-4mar[9] | 298dup289-298 | Tyr62 | Stop codon before Met84 | DOD§ | ||
. | . | . | . | . | Exon 2 mutation (according to NM_002049) . | . | . | . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Patient . | Sex . | Age at diagnosis, mo . | DNA source (blasts in PB/BM, %) . | Karyotype . | RNA . | Last normal GATA1 amino acid . | Consequence of mutation on protein . | Clinical status at last follow-up (time since diagnosis, mo) . | ||
| 1 | F | 17 | PB (84) | 47,XX,+8,+21c[20] | 202delAG | Gly31 | Stop codon before Met84 | DOD (6) | ||
| 2 | M | 22 | PB (24) | 48,XY,del(6)(q21q24),+21,+21c[20] | 296ins19 | Ala61 | Stop codon before Met84 | DOD (4) | ||
| 3 | F | 21 | PB (68) | 47,XX,inv(9)(p11q13)c,+21c[1]/47,XX,idem,der(4)t(1;4) (q23;p15)[17]/47,XX,idem, iso(7)(q10)[2] | IVS2+2T>C | Pro73 | Splice mutant | CCR (77) | ||
| 4 | M | 23 | PB (51) | 47,XY,+21c[18]/48,XY,+8,+21c[1]/49,XY,+8,+12,+21c[1] | 262delG | Pro50 | Stop codon after Met84 | CCR (47) | ||
| 5† | M | 13 | PB (8) | 47,XY,t(2;4)(q37;q28),+21c[20] | 297insA | Ala61 | Stop codon before Met84 | CCR (67) | ||
| 6 | F | 23 | BM (24) | 47,XX,+21c[7]/47,XX,der(7)t(1;7)(q22;p22), +21c[11]/47,XX,dup(1)(q22q44), +21c[2] | 272ins10 | Ala53 | Stop codon before Met84 | CCR (75) | ||
| 7 | M | 23 | BM (41) | 47,XY,+21c[16]/48,XY,+8,+21c[4] | 263del43 | Pro50 | Stop codon after Met84 | CCR(66) | ||
| 8 | F | 15 | PB (98) | 47,XX,+21c[20] | 113A>G | Met1Val | No translation from Met1 | DOD (0)* | ||
| 9 | F | 35 | BM (17) | Not determined | 225C>T† | Pro38Leu | Polymorphism† | CCR (8) | ||
| 11B‡ | M | 11 | BM (20) | 47, XY +21 | 202delAG | Gly31 | Stop codon before Met84 | CCR (29) | ||
| 14 | F | 31 | BM (>20) | 48,XX,+8,+21c[9/25] | 332G>T | Pro73 | Splice mutant | CCR (95) | ||
| 21 | F | 31 | BM (38.5) | 48,XX,+8,+21c[7]/47,XX,+21c[2] | 292ins11 | Leu60 | Stop codon after Met84 | CCR (25) | ||
| 24 | F | 11 | BM (33) | 47,XX,+21c | 115G>A | Met1Ile | No translation from Met1 | CCR (67) | ||
| 25 | M | 44 | BM (55) | 48,XY,+21c,+mar1,+mar2[7]/49,X, -Y,+8,+11,+21c,+mar1[2] | 161C>T | Pro16 | Stop codon before Met84 | CCR (24) | ||
| 26 | F | 20 | BM (23) | 47,XX,+21c[4]/46,XX[2] | 301del11,ins22 | Tyr63 | Stop codon after Met84 | Died of sepsis in CCR (4) | ||
| 48 | M | 26 | BM (40) | 47,XY+21,-11,-13,+3mar | Normal | Ser413 | CCR (19) | |||
| 49† | M | 50 | BM (70) | Not determined | 116G>T | Met1 | Stop codon before Met84 | DOD (34) | ||
| 62B‡ | M | 22 | BM (40) | 41-45,del(X)(p22),Y,-4,add(5)(p15),-7[3],-8,-9[8],-11,-12[8],-15,del(17)(p11),+21c,+der(21)add(21)(p?)?,-22[7]+3-4mar[9] | 298dup289-298 | Tyr62 | Stop codon before Met84 | DOD§ | ||
The French-American-British (FAB) subtype of patient 1's AML was M0; all others were M7. PB indicates peripheral blood; BM, bone marrow; DOD, dead of disease; and CCR, complete clinical remission
DOD at diagnosis
Same mutation identified in one of 50 healthy controls
Previous TMD (samples from the TMD of 2 patients, 11B and 62B, are included in Table 2 as patients 11A and 62A)
Refused treatment