Patients with a homozygous ERCC6L2 mutation
| Family . | Patient . | Disease course . | Age at hematological diagnosis, y . | Previous conditions . | Family history of malignancies . | BM karyotype . | Somatic mutations in BM . | Somatic mutation analysis . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| FLT3/ NPM1 . | TP53, VAF . | Other . | ||||||||
| 1 | 1445 | MDS → AML M6 → relapse soon after allogeneic HSCT; died | MDS at 38; AML M6 at 39 | No | Father died as a result of CRC in his 50s; paternal cousin died of pancreatic cancer in 40s; 1458 | Hypodiploid 41-43, −5, −7 −17, −18, −19, −20 | −/− | c.532C>G p.(His178Asp) 35% | None | Whole-exome sequencing |
| 1 | 1458 | MDS → AML M6 → relapsed on chemotherapy; died | MDS at 36; AML M6 at 37 | Melanoma in situ × 2 (surgery) | Father died as a result of CRC in his 50s; paternal cousin died of pancreatic cancer in 40s; 1445 | Hypodiploid 43, −7, −12, 5q− | −/− | c.517G>A p.(Val173Met) | N/A | Capillary sequencing of TP53 |
| 2 | 1450 | BMF; alive | 14 | No | 2 paternal aunts (1439, 1459) died as a result of AML M6 | CN | −/− | None | None | NGS panel |
| 2 | 1439 | AML M6 → relapsed 13 mo after allogeneic HSCT; died | 59 | No | Sister (1459) died as a result of AML M6; other sister (1463) has BMF | t(3;12;?),t(12;?), −7, −5, t(5;?) | −/− | c.577C>T p.(His193Tyr), c.818G>A p.(Arg273His) | N/A | Capillary sequencing of TP53 |
| 2 | 1459* | AML M6 → refractory disease; died | 38 | No | Sister (1439) died as a result of AML M6; other sister (1463) has BMF | Complex (specific data N/A) | N/A | N/A | N/A | N/A |
| 2 | 1463 | Mild neutropenia and thrombocytopenia → BMF; alive | Cytopenias at 47; BMF at 59 | No | 2 sisters (1459 and 1439) died as a result of AML M6 | CN | −/− | c.743G>A p.(Arg248Gln) 5%, c.830G>T p.(Cys277Phe) 23%, c.843C>A p.(Asp281Glu) 11% | None | NGS panel |
| 3 | 1438 | AA, spontaneous recovery → marginal neutropenia and thrombocytopenia and severe BMF 20 y later | AA at 11; mild cytopenias at 20; BMF at 31 | Cerebral vein thrombosis, Rathke’s cyst | 2 cousins (mother’s side) with some hematological symptoms; grandmother died as a result of leukemia NOS; 6/7 of grandmother’s siblings died of solid tumors; 2/13 of father’s siblings died of cancer (CRC and liver) | CN | −/− | c.659A>G p.(Tyr220Cys) 31% | None | NGS panel |
| 4 | 1443 | AML M6 → relapsed soon after allogeneic HSCT; died | AML M6 at 65 | Tubular adenoma with dysplasia in rectum at 59 | Sister died as a result of AA at 34 | 42-46, del(5)(q31), dup(5)(q31)/t(5;5), −7, 11q23/MLL amplification or translocation, −4 | −/− | c.818G>A p.(Arg273His), c.856G>A p.(Glu286Lys) | N/A | Capillary sequencing of TP53 |
| Family . | Patient . | Disease course . | Age at hematological diagnosis, y . | Previous conditions . | Family history of malignancies . | BM karyotype . | Somatic mutations in BM . | Somatic mutation analysis . | ||
|---|---|---|---|---|---|---|---|---|---|---|
| FLT3/ NPM1 . | TP53, VAF . | Other . | ||||||||
| 1 | 1445 | MDS → AML M6 → relapse soon after allogeneic HSCT; died | MDS at 38; AML M6 at 39 | No | Father died as a result of CRC in his 50s; paternal cousin died of pancreatic cancer in 40s; 1458 | Hypodiploid 41-43, −5, −7 −17, −18, −19, −20 | −/− | c.532C>G p.(His178Asp) 35% | None | Whole-exome sequencing |
| 1 | 1458 | MDS → AML M6 → relapsed on chemotherapy; died | MDS at 36; AML M6 at 37 | Melanoma in situ × 2 (surgery) | Father died as a result of CRC in his 50s; paternal cousin died of pancreatic cancer in 40s; 1445 | Hypodiploid 43, −7, −12, 5q− | −/− | c.517G>A p.(Val173Met) | N/A | Capillary sequencing of TP53 |
| 2 | 1450 | BMF; alive | 14 | No | 2 paternal aunts (1439, 1459) died as a result of AML M6 | CN | −/− | None | None | NGS panel |
| 2 | 1439 | AML M6 → relapsed 13 mo after allogeneic HSCT; died | 59 | No | Sister (1459) died as a result of AML M6; other sister (1463) has BMF | t(3;12;?),t(12;?), −7, −5, t(5;?) | −/− | c.577C>T p.(His193Tyr), c.818G>A p.(Arg273His) | N/A | Capillary sequencing of TP53 |
| 2 | 1459* | AML M6 → refractory disease; died | 38 | No | Sister (1439) died as a result of AML M6; other sister (1463) has BMF | Complex (specific data N/A) | N/A | N/A | N/A | N/A |
| 2 | 1463 | Mild neutropenia and thrombocytopenia → BMF; alive | Cytopenias at 47; BMF at 59 | No | 2 sisters (1459 and 1439) died as a result of AML M6 | CN | −/− | c.743G>A p.(Arg248Gln) 5%, c.830G>T p.(Cys277Phe) 23%, c.843C>A p.(Asp281Glu) 11% | None | NGS panel |
| 3 | 1438 | AA, spontaneous recovery → marginal neutropenia and thrombocytopenia and severe BMF 20 y later | AA at 11; mild cytopenias at 20; BMF at 31 | Cerebral vein thrombosis, Rathke’s cyst | 2 cousins (mother’s side) with some hematological symptoms; grandmother died as a result of leukemia NOS; 6/7 of grandmother’s siblings died of solid tumors; 2/13 of father’s siblings died of cancer (CRC and liver) | CN | −/− | c.659A>G p.(Tyr220Cys) 31% | None | NGS panel |
| 4 | 1443 | AML M6 → relapsed soon after allogeneic HSCT; died | AML M6 at 65 | Tubular adenoma with dysplasia in rectum at 59 | Sister died as a result of AA at 34 | 42-46, del(5)(q31), dup(5)(q31)/t(5;5), −7, 11q23/MLL amplification or translocation, −4 | −/− | c.818G>A p.(Arg273His), c.856G>A p.(Glu286Lys) | N/A | Capillary sequencing of TP53 |
All TP53 mutations reported in NM_000546.5. Variant allele frequency (VAF) not available for capillary sequencing data. Only hotspot exons 5-9 were checked with capillary sequencing (supplemental methods).
AA, aplastic anemia; CN, normal chromosomes; CRC, colorectal cancer; NGS, next-generation sequencing; NOS, not otherwise specified; N/A, not available.
Not tested.