Table 1.
Clinical and genetical descriptions of patients with XP-C with MDS/AML
| Patient number (sex) | ID | Geographic familial origin | XP diagnosis (age) | Mutation on the XPC gene* | Hematological malignancies type (age at diagnosis) | Somatic chromosomal abnormalities† (recurrent bolded) | Somatic mutations‡,¶ (recurrent bolded) | Other clinical information (age) | Familial information (age)§ |
|---|---|---|---|---|---|---|---|---|---|
| 1 (M) | XP10VI | Moroccan | XPC (4 y) | HMZ delTG | AML-4 (27 y) | N/A | N/A | Death resulting from major toxicity after chemotherapy (28 y) | Cousin of patient #2 |
| 1 XP-C brother (death at 6 y) | |||||||||
| 2 (M) | XP82VI | Tunisian | XPC (1.5 y) | HMZ delTG | AML-6 (16 y) | del(5q), monosomy7, del(9q), del(20q) | TP53:p.T284P | RIC HSCT (17 y) | Cousin of patient #1 |
| Death of toxicity with persistent leukemia (18 y) | 1 XP-C brother (death at 23 y) | ||||||||
| 3 (F) | XP235VI | Tunisian | XPC (9 y) | HMZ delTG | RAEB-1 (24y), then RAEB-2 and AML-6 (25 y) | Complex karyotype with del(5q) | TP53:p.E346X and c.672+1G>T (splice); | 5-Aza-C treatment of 3 y | 1 XP brother (death at 18 y) |
| CSF3R:p.P467S c.1959-1G>A c.1576+1G>C c.1071+1G>C | Death (29 y) | ||||||||
| 4 (F) | XP309VI | Moroccan | XPC (2 y) | HMZ delTG | B-ALL and MDS (7 y) | Monosomy 7 | N/A | B-ALL treated by reduced-dose chemotherapy | N/A |
| Death 10 y | |||||||||
| 5 (M)‖ | XP924VI | Moroccan | XPC (4.5 y) | HMZ delTG | T-ALL (12 y) | T-ALL: trisomy 20 | MDS: TP53:p.R280X T-ALL:PHF6 E150* BCOR G1056fs | T-ALL treated by chemotherapy | 1 XP-C brother (13 y) |
| RAEB-1 (13 y) | MDS: del(5q), del(7q) (see Fig. 1B) | RAEB diagnosed during maintenance therapy, treated by 5 Aza-C | |||||||
| AML-6 (15 y) | AML: complex karyotype with additional abnormalities | Death AML-6 (15 y) | |||||||
| 6 (F) | XP185VI | Spanish but North African mutation | XPC (2 y) | HMZ delTG | RAEB-2 (24 y) | Complex karyotype with del(5q), del(7q), del(20q) and subclonal del(4q) | TP53:p.S215R and p.G154V TET2:p.C1193Y | Treatment 5-Aza-C | No sibling |
| AML with MDS-related changes (25 y) | Death from AML (25 y) | ||||||||
| 7 (M) | XP167VI | Algerian | XPC (3 y) and trisomy 21 | HMZ delTG | RAEB-t (25y) and AML (26 y) | N/A | N/A | Numerous skin cancers, eye radiotherapy (11y) | Brother of patient # 12 |
| Death (26y) | XP brother (death at 18 y for unknown reasons) | ||||||||
| Cousin of patient # 13 | |||||||||
| 8 (M) | XPAHVI | Tunisian | XP (4 y) | HMZ delTG | AML (24 y) | Del(7q), trisomy 8, abnormal 21 | N/A | Multiple skin carcinomas | 3 XP-C siblings (24 y, 25 y, 34 y) |
| Curietherapy at 24 y | |||||||||
| Death (25 y) | |||||||||
| 9 (F) | XP673VI | Moroccan | XPC (12 y) | HMZ delTG | T-ALL (21 y) | N/A | NOTCH1:p.R1598P (HD domain) | Multiorgan failure upon infection, antitumoral therapy (22 y) | 1 XP-C brother with astrocytoma at 14 y (30 y) |
| DNMT3A:p.W313* TET2:p.K1438* | |||||||||
| NRAS:p.Q61R | |||||||||
| 10 (M) | XP538VI | Algerian | XPC (4 y) | HMZ delTG | AML (29 y) | Complex karyotype with UPD(17p/TP53), del(4q), del(5q), del(7q), del(13) and dup(21q) | TP53:p.V272M` | Numerous carcinomas on exposed sites | 1 XP-C sister who died at 12 y for unknown reasons but with strong anemia |
| RAD21:c.937+1G>T (splice) | Death (29 y) | ||||||||
| 11 (F) | XP2006VI | Moroccan | XPC (2 y) | HMZ delTG | AML-6 (29 y) 31% blast cells and myelofibrosis in BM | Complex karyotype with del(5q) | N/A | 5-Aza-C; RIC HSCT (29 y, Alive 3 mo+) | 2 XP-C brothers (14 y, 25 y) |
| 12 (F)** | XPGAVI | Algerian | XP (5 y) | N/A but Obligatory HMZ delTG | RAEB-2 (24 y) | N/A | N/A | Death (2 5y) | Sister of patient #7 |
| First cousin of patient #13 | |||||||||
| 13 (M)** | XPGMVI | Algerian | XP (4 y) | N/A but Obligatory HMZ delTG | RAEB-t (27 y) | N/A | N/A | Death (27 y) | First cousin of patients #7 and #12 |
F, female; M, male; N/A, not available; RIC, reduced intensity conditioning regimen.
HMZ delTG refers to the homozygous XPC gene mutation c.1643_1644 delTG; p.Val548AlafsX572 initially described in Soufir et al.4 Note that all patients are from consanguineous families.
According to karyotype and/or CGH-array analysis and/or WES analysis.
After whole-exome sequencing of the tumor, except patient #5 and #9 where T-ALL samples were analyzed with a dedicated T-ALL gene panel.
Reference number of transcripts: XPC, NM_00628.4; TP53, NM_001126112; TET2, NM_001127208; CSF3R, NM_156039; NRAS, NM_002524; DNMT3A, NM_022552; RAD21, NM_006265; BCOR, NM_001123382; PHF6, NM_032458; NOTCH1, NM_017617.
Age of XP siblings at last follow-up or death.
Reported in Hadj-Rabia et al.19
Reported in Berbis et al.20