Table 1.
Description of the series: patients’ medical history and genetic characteristics
| Previously described | N° | Sex | First tumor (age at onset) | Second tumor (age at onset) | Other tumors (age at onset) | Status (FU from 1st BT) | Gene | Mutation 1 | Mutation 2 |
|---|---|---|---|---|---|---|---|---|---|
| 1 | F | HGG (5y) | Dead (0.9y) | PMS2 | c.2007-2A>G, p.? | c.2007-2A>G, p.? | |||
| (14)1 | 2 | F | ADK (21y) | HGG (33y) | ADK (33y) | Dead (0.7y) | PMS2 | c2531C>A, p.Pro844His (VUS) | c2531C>A, p.Pro844His (VUS) |
| (16)1, C072, P13 | 3 | F | ADK (23y) | ADK (26y) | HGG (35y), ADK (36 and 37y) | Dead (4y) | PMS2 | c.137G>T, p.Ser46Ile | c.137G>T, p.Ser46Ile |
| 4. A | M | HGG (11y) | Dead (0.5y) | MSH6 | c.3725G>A, p.Arg1242His (VUS) | c.3725G>A, p.Arg1242His (VUS) | |||
| 4.B | F | HGG (13y) | Dead (0.5y) | MSH6 | c.3725G>A, p.Arg1242His (VUS) | c.3725G>A, p.Arg1242His (VUS) | |||
| 5 | M | HGG (6y) | HGG (7y) | Dead (2.8y) | PMS2 | c.2007-2A>G, p.? | c.2007-2A>G, p.? | ||
| 6 | M | MB (7y) | ADK (22y) | HGG (25y), meningioma | Dead (18.7y) | MSH6 | c.1196C>T, p.Pro399Leu (VUS) | c.2061T>G, p.Cys687Trp (VUS) | |
| (30)1 | 7.A | F | HGG (5y) | Dead (1.8y) | MSH6 | c.1596_1597dup, p.Glu533Valfs*39 | c.3261del, p.Phe1088Serfs*2 | ||
| C142 | 7.B | F | HGG (17y) | Dead (1.3y) | MSH6 | c.1596_1597dup, p.Glu533Valfs*39 | c.3261del, p.Phe1088Serfs*2 | ||
| (12)1, C192 | 8 | F | Osteosarcoma (11y) | HGG (13y) | Dead (0.4y) | PMS2 | c.161T>C, p. Ile54Thr (VUS) | c.1831dup, p.Ile611Asnfs*2 | |
| P93, ID134 | 9 | M | TALL (2y) | HGG (3y) | Alive (CR, 2.1y) | PMS2 | C.2007-2A>G, p.? | C.2007-2A>G, p.? | |
| ID184 | 10 | F | PNET (6y) | ADK (9y) | HGG (14y) | Dead (7.5y) | PMS2 | c.862C>T p.Gln288* | c.862C>T p.Gln288* |
| (31)1, C232 | 11 | M | TLL (7y) | TLL (11y) | HGG (14y), ADK (14y) | Dead (1.9y) | MSH6 | c.1763_1771dup, p.His588_Pro590dup (VUS) | c.1763_1771dup, p.His588_Pro590dup (VUS) |
| (8)1 | 12.A | F | HGG (12y) | TLL (14y) | ADK (14 and 21y) | Dead (9.7y) | PMS2 | c.24-12_107delinsAAAT, p.? | c.1-?_23+?del, p.? |
| (9)1 | 12.B | M | TLL (6y) | HGG (10y) | Dead (2.7y) | PMS2 | c.24-12_107delinsAAAT, p.? | c.1-?_23+?del, p.? | |
| ID144, Pub5 | 13 | F | MB (1y) | Alive (CR, 2.3y) | MSH6 | c.2426_2428del, p.Val809del (VUS) | c.2426_2428del, p.Val809del (VUS) | ||
| (18)1, C10.12 | 14 | M | HGG (6y) | Dead (1.1y) | PMS2 | c.2007-2A>G, p.? | c.2007-2A>G, p.? | ||
| (6)1 | 15 | M | Sarcoma (3y) | HGG (11y) | Burkitt lymphoma (18y), ADK (19y), HGG (20y) | Dead (9.9y) | PMS2 | c.903G>T, p.Lys301Asn | c.1145-?_2174+?dup, p.? |
| (24)1 | 16 | M | HGG (3y) | Dead (0.6y) | MSH2 | c.1-?_1076+?del, p.? | c.454del, p.Met152Cysfs*22 | ||
| (21)1 | 17.A | F | AML (5y) | MB (6y) | Dead (3.7y) | MLH1 | c.199G>T, p.Gly67Trp | c.199G>T, p.Gly67Trp | |
| 17.B | F | HGG (3y) | Dead (0.2y) | MLH1 | c.199G>T, p.Gly67Trp | c.199G>T, p.Gly67Trp | |||
| (5)1, C182 | 18 | M | ADK (22y) | ADK (32y) | HGG (41y) | Dead (1.5y) | PMS2 | c.(988 + 1_9891)_(1144 + 1_1145-1)del, p.(Glu330_Glu381del) | c.2249G>A, p.Gly750Asp (VUS) |
| (2)1, C09.12 | 19 | M | TLL (4y) | HGG (8y) | Alive (CR, 3y) | PMS2 | c.2007-2A>G, p.? | c.2007-2A>G, p.? | |
| 20 | F | HGG (6y) | Dead (0.2y) | MSH2 | c.508C>T, p.Gln170* | c.508C>T, p.Gln170* | |||
| Pub6 | 21 | F | HGG (18y) | Dead (2.2y) | PMS2 | c.686_687del, p.Ser229Cysfs*19 | c.686_687del, p.Ser229Cysfs*19 | ||
| (17)1, C29.12 | 22 | M | HGG (6y) | Dead (0.8y) | PMS2 | c.(2275 + 1_2276-1)_(*160_?)del p.? | c.(2275 + 1_2276-1)_(*160_?)del p.? | ||
| 23 | M | HGG (3y) | Alive (PD, 2.7y) | MSH6 | c.3386_3388delGTG, p.Cys1129_Val1130delinsLeu (VUS) | c.3386_3388delGTG, p.Cys1129_Val1130delinsLeu (VUS) | |||
| 24 | M | HGG (7y) | Dead (0.8y) | PMS2 | c.(705 + 1_706-1)_(803 + 1_804-1)del, p.(Leu236Hisfs*30) | c.(705 + 1_706-1)_(803 + 1_804-1)del, p.(Leu236Hisfs*30) | |||
| (1)1, C052 | 25 | F | HGG (22y) | ADK (25y) | Osteosarcoma (25y), AML (31y) | Dead (10y) | PMS2 | c.400C>T, p.Arg134* | c.1579del, p.Arg527Glyfs*68 |
| 26 | M | BLL (12y) | HGG (13y) | Dead (0.1y) | PMS2 | c.(2275 + 1_2276-1)_(*160_?)del p.? | c.803 + 2T>G, p.? | ||
| 27 | M | HGG (7y) | TLL (9y) | Dead (1.4y) | PMS2 | c.746_753del, p.Asp249Valfs*2 | c.1738A>T, p.Lys580* | ||
| (10)1, C01.22 | 28 | F | HGG (19y) | ADK (24y) | Dead (5.8y) | PMS2 | c.1730dup, p.Arg578Alafs*3 | c.137G>T, p.Ser46Ile | |
| (26)1, C20.22 | 29.A | F | HGG (6y) | Dead (0.3) | MSH6 | c2216C>A, p.Thr739Lys (VUS) | c2216C>A, p.Thr739Lys (VUS) | ||
| (27)1, C20.12 | 29.B | F | HGG (9y) | Dead (0.3y) | MSH6 | c2216C>A, p.Thr739Lys (VUS) | c2216C>A, p.Thr739Lys (VUS) | ||
| 30 | M | HGG (6y) | HGG (6y) | Dead (1.2y) | MSH6 | c.1800_1813dup, p.Thr605Ilefs*10 | c.1800_1813dup, p.Thr605Ilefs*10 | ||
| P53 | 31 | F | HGG (10y) | Alive (CR, 1.8y) | PMS2 | c.634C>T, p.Gln212* | c.1239del, p.Asp414Thrfs*34 | ||
| 32 | F | HGG (13y) | HGG (13y) | Dead (1.1y) | MSH6 | c.2731C>T,p.Arg911* | c.3013C>T, p.Arg1005* | ||
| (121)7 | 33.A | M | HGG (10y) | Dead (9y) | PMS2 | c.137G>T, p.Ser46Ile | c.804-2A>G; p.? | ||
| 33.B | F | ADK (21y) | HGG (24y) | Dead (2.9y) | PMS2 | c.137G>T, p.Ser46Ile | c.804-2A>G; p.? | ||
| (7)1 | 34 | M | HGG (7y) | TLL (7y) | HGG (8y) | Dead (1.4y) | PMS2 | c.2113G>A, p.Glu705Lys (VUS) | c.706-?_903+?del, p.? |
| 35 | M | ADK (12y) | TLL (16y) | HGG (18y) | Dead (2.4y) | PMS2 | c.862C>T, p.Gln288* | c.862C>T, p.Gln288* | |
| (19)1 | 36.A | F | MB (5y) | AML (7y) | Dead (3.7y) | MLH1 | c.678-7_686del, p.? | c.678-7_686del, p.? | |
| (20)1, C152 | 36.B | M | TLL (5y) | HGG (6y) | Dead (1.6y) | MLH1 | c.678-7_686del, p.? | c.678-7_686del, p.? | |
| 37.A | M | HGG (12y) | Dead (1.4y) | PMS2 | c.137G>T, p.Ser46Ile | c.1145?_2174?dup, p.? | |||
| 37.B | F | MB (5y) | Alive (CR, 15y) | PMS2 | c.137G>T, p.Ser46Ile | c.1145?_2174?dup, p.? | |||
| 38.A | F | HGG (6y) | Dead (0.1y) | MSH2 | c.1667T>C, p.Leu556Ser (VUS) | c.1667T>C, p.Leu556Ser (VUS) | |||
| ID204 | 38.B | F | HGG (18y) | Dead (0.6y) | MSH2 | c.1667T>C, p.Leu556Ser(VUS) | c.1667T>C, p.Leu556Ser (VUS) | ||
| ID234 | 38.C | F | ADK (9y) | HGG (20y) | Dead (0.3y) | MSH2 | c.1667T>C, p.Leu556Ser (VUS) | c.1667T>C, p.Leu556Ser (VUS) | |
| ID194 | 38.D | M | ADK (8y) | ADK (8y) | HGG (13y) | Dead (1y) | MSH2 | c.1667T>C, p.Leu556Ser (VUS) | c.1667T>C, p.Leu556Ser (VUS) |
1Lavoine N et al., J Med Genet 2015.
2Bodo S et al., Gastroenterology. 2015.
3Tesch VK et al., Front Immunol. 2018.
4Gallon R et al., Hum. Mutat. 2019.
5Taeubner J et al., Eur J Hum Genet. 2018.
6Baris HN et al., Ped. Blood Cancer, 2016.
7Giunti L et al., J Hum Genet. 2009.
BT: brain tumor, FU: follow-up, y: years, HGG: High-grade glioma, MB: Medulloblastoma, PNET: Primitive neuro-epithelial tumor, ADK: digestive Adenocarcinoma, TALL: T Acute lymphoblastic leukemia, TLL/BLL: T/B lymphoblastic lymphoma, AML: Acute myeloid leukemia, RC: complete remission, PD: progressive disease.