Genotypic and phenotypic features of B-CLL tumors withATM mutations
| Tumor . | ATM protein . | ATM mutation base (amino acid change) . | Germline/ somatic . | TP53 gene . | p53/MDM2/p21 induction . | Nearest VH/D/J family . | % Homology . | Karyotype . | Stage . | Th . |
|---|---|---|---|---|---|---|---|---|---|---|
| B-CLL1 | A | 1058delGT | G | WT | D | V1-02 | 100 | 45XY,-13,der(21)t(13;21) | B | C |
| G5464A(E1822Q) | Acq | D21-9 | (q12;p10)/46XY,add(4)(p1)/ | |||||||
| 46XY | ||||||||||
| B-CLL33 | A | G8600GA (G2867E) | Acq | WT | D | V3-11 | 100 | 46XX,del11q23 | C | E/C |
| Pre-l | ||||||||||
| LOH across ATM | D-39 | |||||||||
| B-CLL34 | A | 2114insA | Acq | WT | D | V3-23 | 99.6 | 46XY,der6;t(6;15)(p23;q14); | C | C |
| Pre-l | D3-16 | der18;t(8;18)(q11;p11) | ||||||||
| 4393insA | Acq | |||||||||
| B-CLL2 | A | G1048T(A350T) | Acq | WT | ND | V1-02 | 100 | ND | C | C/F |
| T1055C(I352T) | Acq | D3-22 | ||||||||
| B-CLL4 | R | G6820A (A2274K) | G | WT | D | V1-69 | 100 | ND | A | No |
| 6277delC | Acq | Dns/J6 | ||||||||
| B-CLL35 | R | A8266T(K2756stop) | G | WT | D | V3-33 | 99.4 | 46XX | B | No |
| D3-3 | ||||||||||
| B-CLL7 | R | G8084C (G2695A) | Acq | WT | D | V3-72 | 100 | 46XY,der(8)add(8)(p23)add | C | C/F/ |
| G7351A (A2451T) | Acq | D2-2 | (8)(q24),del(13)(q14q22)/ | CHOP | ||||||
| J4 | 46XY | |||||||||
| B-CLL36 | N | A8839C (T2947S) | ND | WT | D | V1-69 | 100 | 46XY,del11q23 | C | No |
| LOH across ATM | D2-21 | |||||||||
| B-CLL37 | N | T6055G (Y2019D) | ND | WT | D | V3-48 | 100 | ND | C | C |
| D21-10 | ||||||||||
| BCLL38* | N | C1300T (P434S) | ND | WT | D‡ | V1-46 | 99.3 | 46XY | C | C |
| D3-10 | ||||||||||
| B-CLL39 | N | A6295C(H2099Y) | ND | C1004T | D‡ | V1-69 | 100 | 46XY,del13q14 | B | C |
| (silent) | D3-10 | |||||||||
| B-CLL40 | R | G3556T(E1186stop) | ND | WT | D‡ | V4-59 | 98.9 | ND | C | C |
| D5-12 | ||||||||||
| B-CLL6† | R | 3994ins190 | Acq | WT | N | V3-73 | 100 | ND | A | No |
| B-CLL41 | R | 4829delG | ND | WT | N | V1-46 | 99.1 | ND | B | No |
| Dns | ||||||||||
| B-CLL42 | R | 7511del62 | Acq | WT | N | V3-33 | 99.7 | ND | A | No |
| D3-10 | ||||||||||
| BCLL5 | R | 3910del7 | Acq | WT | N | V3-23 | 99.6 | 46XYdel13q(q12;q32) or | A | No |
| Dns | (q14;q34) |
| Tumor . | ATM protein . | ATM mutation base (amino acid change) . | Germline/ somatic . | TP53 gene . | p53/MDM2/p21 induction . | Nearest VH/D/J family . | % Homology . | Karyotype . | Stage . | Th . |
|---|---|---|---|---|---|---|---|---|---|---|
| B-CLL1 | A | 1058delGT | G | WT | D | V1-02 | 100 | 45XY,-13,der(21)t(13;21) | B | C |
| G5464A(E1822Q) | Acq | D21-9 | (q12;p10)/46XY,add(4)(p1)/ | |||||||
| 46XY | ||||||||||
| B-CLL33 | A | G8600GA (G2867E) | Acq | WT | D | V3-11 | 100 | 46XX,del11q23 | C | E/C |
| Pre-l | ||||||||||
| LOH across ATM | D-39 | |||||||||
| B-CLL34 | A | 2114insA | Acq | WT | D | V3-23 | 99.6 | 46XY,der6;t(6;15)(p23;q14); | C | C |
| Pre-l | D3-16 | der18;t(8;18)(q11;p11) | ||||||||
| 4393insA | Acq | |||||||||
| B-CLL2 | A | G1048T(A350T) | Acq | WT | ND | V1-02 | 100 | ND | C | C/F |
| T1055C(I352T) | Acq | D3-22 | ||||||||
| B-CLL4 | R | G6820A (A2274K) | G | WT | D | V1-69 | 100 | ND | A | No |
| 6277delC | Acq | Dns/J6 | ||||||||
| B-CLL35 | R | A8266T(K2756stop) | G | WT | D | V3-33 | 99.4 | 46XX | B | No |
| D3-3 | ||||||||||
| B-CLL7 | R | G8084C (G2695A) | Acq | WT | D | V3-72 | 100 | 46XY,der(8)add(8)(p23)add | C | C/F/ |
| G7351A (A2451T) | Acq | D2-2 | (8)(q24),del(13)(q14q22)/ | CHOP | ||||||
| J4 | 46XY | |||||||||
| B-CLL36 | N | A8839C (T2947S) | ND | WT | D | V1-69 | 100 | 46XY,del11q23 | C | No |
| LOH across ATM | D2-21 | |||||||||
| B-CLL37 | N | T6055G (Y2019D) | ND | WT | D | V3-48 | 100 | ND | C | C |
| D21-10 | ||||||||||
| BCLL38* | N | C1300T (P434S) | ND | WT | D‡ | V1-46 | 99.3 | 46XY | C | C |
| D3-10 | ||||||||||
| B-CLL39 | N | A6295C(H2099Y) | ND | C1004T | D‡ | V1-69 | 100 | 46XY,del13q14 | B | C |
| (silent) | D3-10 | |||||||||
| B-CLL40 | R | G3556T(E1186stop) | ND | WT | D‡ | V4-59 | 98.9 | ND | C | C |
| D5-12 | ||||||||||
| B-CLL6† | R | 3994ins190 | Acq | WT | N | V3-73 | 100 | ND | A | No |
| B-CLL41 | R | 4829delG | ND | WT | N | V1-46 | 99.1 | ND | B | No |
| Dns | ||||||||||
| B-CLL42 | R | 7511del62 | Acq | WT | N | V3-33 | 99.7 | ND | A | No |
| D3-10 | ||||||||||
| BCLL5 | R | 3910del7 | Acq | WT | N | V3-23 | 99.6 | 46XYdel13q(q12;q32) or | A | No |
| Dns | (q14;q34) |
B-CLL 38 also has sequence change A1704G (silent).
B-CLL 6 also has sequence change C3161G (P1054R), a rare polymorphism, observed in breast tumors.
B-CLLs 38, 39, and 40 showed a normal induction of p53, but defective induction of MDM2 and p21 following IR. WT indicates wild type; ND, not done; A, absent; R, reduced; N, normal; D, defective; Acq, acquired; G, germline; Pre-l, prelymphoid; ns, not specified; Th, previous therapy; C, chlorambucil; P, prednisolone; CHOP, cyclophosphomide, doxorubicin, vincristine, and prednisolone; F, fludarabine; E, etoposide; and No, no previous therapy given; LOH, loss of heterozygosity.