Table 1. Overview of the study population.
ID number 12-04-079 | Rel. | CLINICAL CHARACTERISTICS | gene | MMR MUTATION | LOE IHC## | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age of EC diagnosis | Type EC | grade EC | stage EC | MSI$ | Other tumor sites** | cancer phenotype | DNA change | protein change | LOVD ID*** | NGS confirmed | ||||
11 | D | 38 | endometrioid | 1 | 1a | I | poor | MSH2 | c.244A >T | p.Lys82* | MSH2_00750 | YES | na | |
12 | D | 46 | endometrioid | 3 | 1b | S | poor | MSH2 | c.244A >T | p.Lys82* | MSH2_00750 | YES | na | |
16 | D | 38 | na | na | na | na | C-29;C-43 | poor | MSH2 | c.244A >T | p.Lys82* | MSH2_00750 | YES | na |
17 | E | 46 | endometrioid | na | na | S | poor | MSH2 | c.212–2A >G | splice alteration | MSH2_000724 | YES | na | |
19 | E | 53 | na | na | na | na | neutral | MSH2 | c.212–2A >G | splice alteration | MSH2_000724 | YES | na | |
26 | F | 49 | endometrioid | 1 | 1a | na | poor | MSH6 | c.1139_1143delATGAG | p.Asp380Alafs*6 | MSH6_008335 | YES | na | |
28 | F | 55 | endometrioid | 1 | 1b | na | neutral | MSH6 | c.1139_1143delATGAG | p.Asp380Alafs*7 | MSH6_008335 | YES | na | |
18 | G | 44 | endometrioid | 1 | na | I | poor | MLH1 | c. 2149_2195dupl | p.His733Asnfs*66 | MLH1_00830 | NO1 | na | |
29 | G | 39 | na | na | na | na | O-na | poor | MLH1 | c. 2149_2195dupl | p.His733Asnfs*66 | MLH1_00830 | NO1 | na |
2 | A | 52 | endometrioid | 2 | 1b | S | neutral | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | na | |
3 | A | 65 | serous | 3 | 1c | I | C-59 | poor | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | Y |
6^ | B | 51 | endometrioid | 1 | 1b | S | neutral | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | na | |
7 | B | 62 | endometrioid | 3 | 2 | I | C-70;U-81 | poor | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | Y |
8 | C | 54 | endometrioid | 1 | 1a | I | neutral | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | Y | |
9 | C | 52 | endometrioid | 1 | 1 | S | B-na | poor | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | na |
1 | - | 50 | endometrioid | 1 | 2 | I | neutral | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | Y | |
4 | - | 57 | endometrioid | 3 | na | I | neutral | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | Y | |
5 | - | 62 | endometrioid | 1 | 1b | I | neutral | MSH6 | c.3729_3732dupATTA | p.Phe1245llefs*313 | MSH6_00330 | YES | Y | |
10 | - | 40 | endometrioid | 1 | na | na | O-40 | poor | MSH6 | c.1444 C >T | p.Arg482* | MSH6_000666 | YES | na |
13 | - | 81 | na | na | na | na | C-59 | poor | PMS2 | c.989–296_1144+706del | p.Glu330_Glu381del | PMS2_00039 | NO1 | na |
14 | - | 31 | na | na | na | na | poor | MSH6 | c.3772 C >T | p.Gln1258* | MSH6_002597 | YES | na | |
15^ | - | 49 | endometrioid | 1 | 3 | S | O-49 | poor | MSH6 | c.2569_2572del | p.Asp857Phefs10* | MSH6_00326 | YES | Y |
20 | - | 56 | endometrioid | na | na | S | B-50 | poor | MSH6 | c.2191C >T | p.Gln731* | MSH6_000928 | YES | na |
21 | - | 58 | endometrioid | 1 | 1b | I | C-58 | poor | MLH1 | c.901C >T | p.Gln301* | MLH1_00407 | YES | Y |
22 | - | 60 | endometrioid | 1 | 3 | na | neutral | MSH6 | c.2815 C >T | p.Gln939* | MSH6_00465 | # | na | |
23 | - | 49 | endometrioid | 1 | 1b | I | poor | PMS2 | c.24–12_107del96 | p.Ser8Argfs5* | PMS_00205 | NO1 | Y | |
24 | - | 61 | endometrioid | 3 | 1b | I | C-56 | poor | MSH6 | c.4002–22_4002–4del19 | splice alteration | MSH6_00335 | YES | Y |
25 | - | 44 | endometrioid | 1 | na | I | poor | MSH6 | c.3838C >T | pGln1280* | MSH6_00554 | # | Y | |
27 | - | 40 | na | na | na | S | poor | MSH2 | c.212-?_366+?del | p.Ala72Phefs*9 | MSH2_00076 | NO1 | na | |
30 | - | 71 | endometrioid | 2 | 3 | I | neutral | MSH2 | c.646–2A >G | splice alteration | MSH2_00751 | NO2 | na | |
31 | - | 50 | mixed | 3 | 1b | I | neutral | MSH6 | c.2191C >T | p.Gln731* | MSH6_00092 | YES | Y | |
32 | - | 64 | endometrioid | 1 | 1a | S | neutral | MSH6 | c.2926_2929dupCGTT | p.Tyr977Serfs*8 | non-deposited | YES | Y | |
33 | - | 49 | endometrioid | 1 | 1b | I | poor | MSH6 | c.1804_1805del2 | p.Ser602Lysfs*4 | non-deposited | YES | Y | |
34 | - | 75 | endometrioid | 1 | 1b | na | C-na | poor | MSH6 | c.3794_3801del8 | p.His1266Metfs*6 | non-deposited | YES | na |
35 | - | 64 | endometrioid | 1 | 1b | I | neutral | MSH6 | c.3949_3965del17 | p.His1317Ilefs*2 | non-deposited | NO1 | Y | |
37 | - | 53 | na | na | na | na | C-52 | poor | MSH2 | c.1203dup | p.Gln402Thrfs*15 | MSH2_00896 | YES | na |
38 | - | 55 | endometrioid | 2 | 1 | I | neutral | MSH6 | c.3185G >T | p.Cys1062Phe | MSH6_00885 | NO2 | na |
Rel.: the same letters indicate a familial relationship.
MSI: microsatellite instability in endometrial cancer specimen. S= stable; I = instable.
C-n = colorectal cancer-age at diagnosis; O-n = ovarian cancer-age at diagnosis; B-n = breast cancer-age at diagnosis; U-n = tumor of urinary tract-age at diagnosis.
LOVD ID: mutation is deposited with the indicated number in the Leiden Open Variation Database.
NGS was of poor quality and sample was excluded from further analyses.
LOE of MMR: loss of expression of MMR protein in endometrial cancer specimen. Y = loss of expression; N = no expression loss.
samples were subjected to NGS twice to assess reproducibility.
large rearrangements could not be detected by our pipeline.
no sufficient coverage of the specific region in this sample.
this is a founder mutation.
Mutations are also deposited in the dbSNP database: 4 = rs267607917; 5 = rs142111387; 6 = rs63750909; 7 = rs63750554; 8 = rs63751442.
na: non-available/non-analyzed.