Features of the 16 FA individuals with CMEs
| Sample . | Genetic group . | CMEs (size in Mb) . | Start (Mb) . | End (Mb) . | Cell fraction (%) . | Age at DNA sampling (y) . | Clinical features (age at BMF in y) . | Years from DNA sampling to cancer . | Cancer diagnosis (age in y) . | Evolution (age in y) . | Cause of death . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| FA466 | A | UPD 4p (6.6) | pter | 6.6 | 9 | 0.7 | BRH, CaLS, BMF (0.7) | — | None | Alive (8) | — |
| FA106 | A | UPD 6p (26.1) | pter | 26.1 | 13 | 15 | BMF (8) | — | None | Exitus (22) | H1N1 viral infection |
| FA117 | A | UPD 10q (70.4) | 65.1 | qter | 17 | 30 | BMF (8) | 6 | AML (36) | Exitus (36) | BM transplant complications |
| FA648 | A | Gain 1q (104.3)* | cen | qter | 29 | 32 | BRH, ID, KM, BMF (32) | 0 | Lymphoma (32) | Exitus (32) | Lymphoma |
| 041607 | A | Monosomy 7 (159.1) | pter | qter | 59 | 50 | GR, BMF (23) | 0 | Breast (37,45), AML (50) | Exitus (50) | AML |
| FA647 | A | Gain 3q (36.3)† | 161.5 | qter | 30 | 4 | GIM, BMF (4) | 1 | MDS (5) | Exitus (5) | BMF |
| Loss 5q (49.3)† | 131.4 | qter | 32 | ||||||||
| EGF058 | A | Gain 1q (76.7) | cen | 222.8 | 59 | 23 | GR, BMF (23) | 8 | HNSCC (31) | Exitus (31) | Cancer treatment toxicity |
| Gain 3q (64.7) | 133.1 | qter | 27 | ||||||||
| FA013 | A | UPD 6p (32.7) | pter | 32.7 | 28 | 24 | BRH, CaLS, BMF (7) | 10 | Anal SCC (34) | Exitus (35) | Metastatic Anal SCC |
| Gain 6p (22.8) | 32.7 | 55.5 | 27 | ||||||||
| FA360 | A | Gain 1q (102.7)† | cen | qter | 76 | 30 | BMF (13) | 0 | AML (30) | Exitus (30) | Multiorganic failure after HSCT |
| Loss 11q (30.4)† | 104.5 | qter | 87 | ||||||||
| Trisomy 8 (146.1) | pter | qter | 26 | ||||||||
| Trisomy 9 (141.0) | pter | qter | 27 | ||||||||
| 041869 | A | Gain 1p (33.5) | 18.5 | 52.0 | 45 | 39 | GR, BRH, CaLS, KM, BMF (8) | 5 | Vulvar SCC (27), esophagus SCC (44) | Exitus (44) | Esophagus SCC |
| Gain 1q (105.9)* | cen | qter | 45 | ||||||||
| Loss 7q (11.1) | 148.0 | qter | 48 | ||||||||
| Loss 8p (4.4) | pter | 4.4 | 32 | ||||||||
| FA178 | A | Loss 1p (29.6) | pter | 29.6 | 41 | 19 | CaLS, UHM, BMF (9) | 0 | AML (19) | Exitus (19) | AML therapy complications (sepsis) |
| Gain 1p (25.8) | 29.6 | 55.4 | 39 | ||||||||
| Gain 3q (63.1)* | 134.7 | qter | 51 | ||||||||
| Loss 5q (98.7) | 82.0 | qter | 38 | ||||||||
| Loss 18q (8.8) | 69.2 | qter | 42 | ||||||||
| FA351 | C | Loss 3p (4.1) | pter | 4.1 | 29 | 2.7 | BMF (2.7) | 0.3 | AML (3) | Exitus (3) | AML therapy complications (multiorganic failure) |
| Gain 3q (18.5) | 159.7 | 178.7 | 69 | ||||||||
| Gain 3q (18.9)* | 178.8 | qter | 62 | ||||||||
| Loss 4p (12.3) | pter | 12.3 | 50 | ||||||||
| Loss 6p (28.6) | pter | 28.6 | 16 | ||||||||
| Loss 6q (63.8) | 107.1 | qter | 80 | ||||||||
| Loss 7p (57.5) | pter | 57.5 | 42 | ||||||||
| Loss 7q (15.3) | 143.8 | qter | 75 | ||||||||
| Gain 8q (20.6) | 56.1 | 76.7 | 26 | ||||||||
| Gain 8q (16.9) | 76.7 | 94.1 | 56 | ||||||||
| Gain 8q (52.0) | 94.2 | qter | 32 | ||||||||
| Gain 13q (93.4) | 21.7 | qter | 19 | ||||||||
| UPD 16p (29.7) | pter | 29.7 | 73 | ||||||||
| Loss 18q (20.7) | 57.4 | qter | 36 | ||||||||
| Gain 21q (12.0) | 36.1 | qter | 29 | ||||||||
| Gain Xp (42.7) | pter | 42.7 | 40 | ||||||||
| 110243 | D2 | UPD 3p (53.6) | pter | 53.6 | 27 | 22 | GR, BRH, HL, ID, KM, BMF (9) | — | None | Alive (27) | — |
| FA531 | D2 | Loss 1p (21.2) | pter | 21.2 | 14 | 26 | GR, BRH | — | None | Alive (28) | — |
| 000644 (+) | D2 | Monosomy 7 (159.1) | pter | qter | 27 | 27 | GR, BRH | 0 | Vulvar SCC (23), oral premalignant findings (24), AML (27) | Alive (37) | — |
| Loss 12p (27.1)‡ | pter | 27.1 | 27 | ||||||||
| Gain 20p (30.8)‡ | pter | 30.8 | 27 | ||||||||
| Loss 20q (20.6)‡ | 30.8 | 51.4 | 27 | ||||||||
| Gain 20q (11.5)‡ | 51.4 | qter | 27 | ||||||||
| FA072 | J | Gain 1q (105.8)* | cen | qter | 66 | 28 | CaLS, CM, BMF (20) | 2 | AML (30) | Exitus (31) | AML therapy complications (pneumonia) |
| Gain 3q (33.6)* | 164.2 | qter | 98 | ||||||||
| Loss 6p (29.9)† | pter | 29.9 | 51 | ||||||||
| Gain 16p (22.6)† | pter | 22.6 | 44 |
| Sample . | Genetic group . | CMEs (size in Mb) . | Start (Mb) . | End (Mb) . | Cell fraction (%) . | Age at DNA sampling (y) . | Clinical features (age at BMF in y) . | Years from DNA sampling to cancer . | Cancer diagnosis (age in y) . | Evolution (age in y) . | Cause of death . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| FA466 | A | UPD 4p (6.6) | pter | 6.6 | 9 | 0.7 | BRH, CaLS, BMF (0.7) | — | None | Alive (8) | — |
| FA106 | A | UPD 6p (26.1) | pter | 26.1 | 13 | 15 | BMF (8) | — | None | Exitus (22) | H1N1 viral infection |
| FA117 | A | UPD 10q (70.4) | 65.1 | qter | 17 | 30 | BMF (8) | 6 | AML (36) | Exitus (36) | BM transplant complications |
| FA648 | A | Gain 1q (104.3)* | cen | qter | 29 | 32 | BRH, ID, KM, BMF (32) | 0 | Lymphoma (32) | Exitus (32) | Lymphoma |
| 041607 | A | Monosomy 7 (159.1) | pter | qter | 59 | 50 | GR, BMF (23) | 0 | Breast (37,45), AML (50) | Exitus (50) | AML |
| FA647 | A | Gain 3q (36.3)† | 161.5 | qter | 30 | 4 | GIM, BMF (4) | 1 | MDS (5) | Exitus (5) | BMF |
| Loss 5q (49.3)† | 131.4 | qter | 32 | ||||||||
| EGF058 | A | Gain 1q (76.7) | cen | 222.8 | 59 | 23 | GR, BMF (23) | 8 | HNSCC (31) | Exitus (31) | Cancer treatment toxicity |
| Gain 3q (64.7) | 133.1 | qter | 27 | ||||||||
| FA013 | A | UPD 6p (32.7) | pter | 32.7 | 28 | 24 | BRH, CaLS, BMF (7) | 10 | Anal SCC (34) | Exitus (35) | Metastatic Anal SCC |
| Gain 6p (22.8) | 32.7 | 55.5 | 27 | ||||||||
| FA360 | A | Gain 1q (102.7)† | cen | qter | 76 | 30 | BMF (13) | 0 | AML (30) | Exitus (30) | Multiorganic failure after HSCT |
| Loss 11q (30.4)† | 104.5 | qter | 87 | ||||||||
| Trisomy 8 (146.1) | pter | qter | 26 | ||||||||
| Trisomy 9 (141.0) | pter | qter | 27 | ||||||||
| 041869 | A | Gain 1p (33.5) | 18.5 | 52.0 | 45 | 39 | GR, BRH, CaLS, KM, BMF (8) | 5 | Vulvar SCC (27), esophagus SCC (44) | Exitus (44) | Esophagus SCC |
| Gain 1q (105.9)* | cen | qter | 45 | ||||||||
| Loss 7q (11.1) | 148.0 | qter | 48 | ||||||||
| Loss 8p (4.4) | pter | 4.4 | 32 | ||||||||
| FA178 | A | Loss 1p (29.6) | pter | 29.6 | 41 | 19 | CaLS, UHM, BMF (9) | 0 | AML (19) | Exitus (19) | AML therapy complications (sepsis) |
| Gain 1p (25.8) | 29.6 | 55.4 | 39 | ||||||||
| Gain 3q (63.1)* | 134.7 | qter | 51 | ||||||||
| Loss 5q (98.7) | 82.0 | qter | 38 | ||||||||
| Loss 18q (8.8) | 69.2 | qter | 42 | ||||||||
| FA351 | C | Loss 3p (4.1) | pter | 4.1 | 29 | 2.7 | BMF (2.7) | 0.3 | AML (3) | Exitus (3) | AML therapy complications (multiorganic failure) |
| Gain 3q (18.5) | 159.7 | 178.7 | 69 | ||||||||
| Gain 3q (18.9)* | 178.8 | qter | 62 | ||||||||
| Loss 4p (12.3) | pter | 12.3 | 50 | ||||||||
| Loss 6p (28.6) | pter | 28.6 | 16 | ||||||||
| Loss 6q (63.8) | 107.1 | qter | 80 | ||||||||
| Loss 7p (57.5) | pter | 57.5 | 42 | ||||||||
| Loss 7q (15.3) | 143.8 | qter | 75 | ||||||||
| Gain 8q (20.6) | 56.1 | 76.7 | 26 | ||||||||
| Gain 8q (16.9) | 76.7 | 94.1 | 56 | ||||||||
| Gain 8q (52.0) | 94.2 | qter | 32 | ||||||||
| Gain 13q (93.4) | 21.7 | qter | 19 | ||||||||
| UPD 16p (29.7) | pter | 29.7 | 73 | ||||||||
| Loss 18q (20.7) | 57.4 | qter | 36 | ||||||||
| Gain 21q (12.0) | 36.1 | qter | 29 | ||||||||
| Gain Xp (42.7) | pter | 42.7 | 40 | ||||||||
| 110243 | D2 | UPD 3p (53.6) | pter | 53.6 | 27 | 22 | GR, BRH, HL, ID, KM, BMF (9) | — | None | Alive (27) | — |
| FA531 | D2 | Loss 1p (21.2) | pter | 21.2 | 14 | 26 | GR, BRH | — | None | Alive (28) | — |
| 000644 (+) | D2 | Monosomy 7 (159.1) | pter | qter | 27 | 27 | GR, BRH | 0 | Vulvar SCC (23), oral premalignant findings (24), AML (27) | Alive (37) | — |
| Loss 12p (27.1)‡ | pter | 27.1 | 27 | ||||||||
| Gain 20p (30.8)‡ | pter | 30.8 | 27 | ||||||||
| Loss 20q (20.6)‡ | 30.8 | 51.4 | 27 | ||||||||
| Gain 20q (11.5)‡ | 51.4 | qter | 27 | ||||||||
| FA072 | J | Gain 1q (105.8)* | cen | qter | 66 | 28 | CaLS, CM, BMF (20) | 2 | AML (30) | Exitus (31) | AML therapy complications (pneumonia) |
| Gain 3q (33.6)* | 164.2 | qter | 98 | ||||||||
| Loss 6p (29.9)† | pter | 29.9 | 51 | ||||||||
| Gain 16p (22.6)† | pter | 22.6 | 44 |
Columns contain information about patient, genetic group, detected CMEs including genomic location and type, start and end of each rearrangement and the estimated proportion of affected cells, the age at DNA sampling and BMF, the main clinical features, the years from sampling to the first cancer diagnosis, the type of cancer and the evolution including cause of death. (+) A single case with CMEs, 000644, presented reverse mosaicism of the FA mutation in blood. The rearrangements detected by SNP array in blood also found by cytogenetic analysis of BM aspirates are shown in bold and italic letters.
AML, acute myeloid leukemia; BM, bone marrow; BMF, bone marrow failure; BRH, bilateral radial hypoaplasia; CaLS: café-au-lait spot; cen, centromere; CM, cardiac malformation; GIM, gastrointestinal malformation; GR, growth restriction; HL, hearing loss; HNSCC, head and neck squamous cell carcinoma; HSCT, hematopoietic stem cells transplantation; ID, intellectual disability; KM, kidney malformation; MDS, myeloid dysplastic syndrome; NoM: no relevant malformation; pter, p terminal; qter: q terminal; UHM, unilateral hand malformation.
Gains of >1 extra copy (triplication-tetrasomy).
Possible unbalanced translocation.
Complex rearrangements.