Table 1. Molecular laboratory tests results and patient characteristics of 76 patients with a pathogenic germline mutation in MLH1, PMS2, MSH2, or MSH6.
| No. | S | Germline mutation | MSI | Meth | IHC | Tumour tested for MSI | Age | Other tumour(s) | AC | 2fam |
|---|---|---|---|---|---|---|---|---|---|---|
| MLH1 | ||||||||||
| 8 | 1 | c.15_28del (p.Gly6fs) | NT | NT | NT | 42 | co42,co47 | + | + | |
| 288 | 2 | c.18_34del (p.Val7fs) | + | − | MLH1/PMS2− | Caecum | 40 | − | − | − |
| 189 | 2 | c.211_213del (p.Glu71del) | + | − | PMS2/MSH6− | Endometrium | 39 | − | − | − |
| 118 | 1 | c.299C>T (p.Arg100X) | NT | NT | NT | 26 | co26,co37 | + | + | |
| 645 | 2 | c.578C>G (p.Ser193X) | + | − | MLH1/PMS2− | Caecum | 26 | co37,co39 | − | + |
| 163 | 1 | c.588+3_588+6del (affects ss) | NT | NT | NT | 50 | co50,co50,co50 | + | + | |
| 198 | 2 | c.677G>A (p.Arg226Gln) (affects ss) | + | − | MLH1/PMS2− | Colon descendens | 41 | − | + | + |
| 318 | 2 | c.806C>G (p.Ser269X) | + | − | MLH1/PMS2− | Colon transversum | 59 | en49,co27 | − | + |
| 19 | 1 | c.806C>G (p.Ser269X) | NT | NT | NT | 45 | co45 | + | + | |
| 345 | 2 | c.1225C>T (p.Gln409X) | + | − | MLH1/PMS2− | Sigmoid | 44 | − | + | + |
| 454 | 2 | c.1354del (p.Thr452fs) | + | − | MLH1/PMS2− | Colon transversum | 49 | − | + | + |
| 335 | 2 | c.1549G>T (p.Gly517X) | + | − | MLH1/PMS2− | Sigmoid | 49 | − | + | + |
| 734 | 2 | c.1852_1854del (p.Lys618del) | + | NT | MLH1/PMS2− | Urothelial cell carcinoma | 60 | co40,en54 | − | + |
| 428 | 2 | c.1852_1854del (p.Lys618del) | + | NT | MLH1/PMS2− | Caecum | 50 | + | + | |
| 15 | 1 | c.1852_1854del (p.Lys618del) | + | NT | MLH1/PMS2− | Endometrium | 52 | ov52,co52 | − | + |
| 451 | 2 | c.1852_1854del (p.Lys618del)a | + | − | MLH1na/PMS2− | Colon ascendens | 27 | − | − | − |
| 168 | 2 | c.1852_1854del (p.Lys618del) | + | NT | NT | Caecum | 42 | − | + | + |
| 42 | 1 | c.1852_1854del (p.Lys618del) | NT | NT | NT | 36 | co36 | + | + | |
| 3 | 1 | c.1852_1854del (p.Lys618del) | + | NT | NT | Colon NOS | 32 | − | + | + |
| 324 | 2 | c.2103+1G>A | + | − | MLH1/PMS2− | Flexura linealis | 50 | co50 | + | + |
| 392 | 2 | c.2103+1G>A | + | − | MLH1/PMS2− | Colon ascendens | 38 | − | + | + |
| 65 | 1 | c.2103+1G>A | + | − | MLH1/PMS2− | Rectum | 42 | − | + | + |
| 222 | 1 | c.2103+1G>A | NT | NT | NT | 38 | co38 | + | + | |
| 260 | 1 | c.2103+1G>A | NT | NT | NT | 55 | co55,en61 | + | + | |
| PMS2 | ||||||||||
| 386 | 2 | entire gene deletion | + | − | PMS2− | Colon ascendens | 36 | − | − | − |
| 641 | 2 | c.989–296_1144+706del | + | NT | PMS2− | Trichoepithelioma/trichoblastoma | 45 | − | − | − |
| MSH2 | ||||||||||
| 322 | 2 | c.1-?_211+?del | + | NT | MSH2/MSH6− | Colon ascendens | 58 | ur49 | + | + |
| 92 | 1 | c.1-?_211+?del | + | NT | MSH2/MSH6− | Endometrium | 41 | − | + | + |
| 5 | 1 | c.1-?_211+?del | + | NT | NT | 38 | co42 | + | + | |
| 614 | 2 | c.1-?_366+?del | + | NT | MSH2/MSH6− | Flexura lienalis | 21 | − | − | − |
| 730 | 2 | c.1-?_1076+?del | + | NT | MSH2/MSH6− | Urothelial cell carcinoma | 57 | co42 | + | + |
| 528 | 2 | c.1-?_1076+?delb | + | NT | none− | Caecum | 32 | en44 | − | + |
| 139 | 1 | c.1-?_1076+?del | + | NT | MSH2/MSH6− | Endometrium | 41 | co42 | + | + |
| 287 | 2 | c.1-?_1276+?del | + | − | MSH2/MSH6− | Caecum | 33 | − | + | + |
| 700 | 2 | c.212–1G>A | + | NT | MSH2-/MSH6na | Caecum | 52 | co61 | − | + |
| 350 | 2 | c.212-?_366+?del | + | − | MSH6− | Caecum | 72 | − | + | + |
| 117 | 1 | c.212-?_366+?del | + | − | MSH2/MSH6− | Ileocecum | 48 | − | + | + |
| 73 | 1 | c.212-?_366+?del | + | NT | NT | Colon ascendens | 44 | en37,ov37 | + | + |
| 237 | 2 | c.255dup (p.Glu86X) | + | NT | MSH2/MSH6− | Sebaceuous gland carcinoma | 39 | co25 | + | + |
| 190 | 2 | c.367-?_645+?del | + | − | MSH2/MSH6− | Caecum | 50 | co50,co50 | − | − |
| 210 | 2 | c.367-?_645+?del | + | − | MSH2/MSH6− | Colon transversum | 43 | − | + | + |
| 366 | 2 | c.642_645del (p.Gln215X) | + | NT | MSH2/MSH6− | Flexura linealis | 46 | − | + | + |
| 18 | 1 | c.793-?_1076+?del | + | − | MSH2/MSH6− | Rectum | 29 | co29 | + | + |
| 25 | 1 | c.836del (p.Leu279fs)c | + | − | MSH2/MSH6− | Flexura linealis | 46 | − | + | + |
| 37 | 1 | c.862C>T (p.Gln288X) | NT | NT | NT | 26 | co26 | + | + | |
| 196 | 2 | c.915_922dup (p.Arg308fs) | + | NT | MSH2/MSH6− | Sigmoid | 46 | co46 | − | − |
| 11 | 1 | c.943-?_1076+?del | + | − | MSH2/MSH6− | Endometrium | 45 | − | + | + |
| 14 | 1 | c.1147C>T (p.Arg383X) | NT | NT | NT | 33 | en33,co50 | + | + | |
| 497 | 2 | c.1165C>T (p.Arg389X) | + | NT | MSH2−/MSH6na | Flexura lienalis | 44 | − | − | − |
| 462 | 2 | c.1203dup (p.Gln402fs) | + | − | MSH2/MSH6− | Sigmoid | 37 | − | + | + |
| 74 | 1 | c.1203dup (p.Gln402fs) | + | − | MSH2−/MSH6na | Rectum | 32 | − | + | + |
| 654 | 1 | c.1255C>T (p.Gln419X) | NT | NT | NT | 45 | co45,co63 | + | + | |
| 301 | 2 | c.1277–2A>G | + | NT | MSH2/MSH6− | Caecum | 33 | − | − | + |
| 637 | 2 | c.1386+1G>T | + | − | MSH2/MSH6− | Colon transversum | 47 | co42 | − | + |
| 625 | 2 | c.1387-?_1510+?del | + | − | MSH2/MSH6− | Endometrium | 45 | co53 | + | + |
| 107 | 1 | c.1494dup (p.Ala499fs) | NT | NT | NT | 46 | co46 | + | + | |
| 327 | 2 | c.1861C>T (p.Arg621X) | + | NT | MSH2/MSH6− | Sigmoid | 58 | − | − | − |
| 480 | 1 | c.2005+1G>C | − | NT | none− | Endometrium | 39 | co45 | + | + |
| MSH6 | ||||||||||
| 206 | 1 | c.1-?_457+?deld | + | NT | MSH6− | Urothelial cell carcinoma | 56 | ur57 | − | + |
| 657 | 2 | c.261-?_457+?dupd | + | NT | MSH6− | Colon descendens | 42 | − | + | + |
| 745 | 2 | c.467C>G (p.Ser156X) | + | − | MSH6− | Ileocecum | 63 | − | + | + |
| 138 | 2 | c.651dup (p.Lys218X)d | + | − | MSH6− | Sigmoid | 52 | en37 | + | + |
| 342 | 1 | c.814G>T (p.Glu272X)d,f | + | − | MSH6− | Endometrium | 57 | − | + | + |
| 338 | 2 | c.1135_1139del (p.Arg379X)d | + | − | MSH6− | Endometrium | 38 | ov38 | − | − |
| 137 | 1 | c.1784del (p.Leu595fs) | − | NT | none− | Rectum | 51 | + | + | |
| 515 | 2 | c.2815C>T (p.Gln939X)a,d | + | NT | MSH6− | Iieum | 65 | co38,co51,co58,ur69 | − | + |
| 105 | 1 | c.3261del (p.Phe1088fs)d | + | − | MSH6− | Colon ascendens | 39 | − | + | + |
| 766 | 2 | c.3261del (p.Phe1088fs) | + | − | MSH6− | Endometrium | 41 | − | − | − |
| 446 | 2 | c.3261dup (p.Phe1088fs)d | + | − | MSH2/MSH6− | Endometrium | 43 | − | + | + |
| 450 | 2 | c.3273dup (p.Lys1092X)d | + | − | MSH6− | Colon ascendens | 50 | co46,co50 | + | + |
| 711 | 2 | c.3438+1G>A | + | NT | MSH6na | Rectum | 45 | − | + | + |
| 692 | 2 | c.3438+1G>A | + | NT | MSH6na | Colon transversum | 43 | en53,ov43 | − | − |
| 500 | 2 | c.3514dup (p.Arg1172fs) | + | + | MSH6− | Colon transversum | 70 | ur70 | − | − |
| 434 | 1 | c.3678_3706dup (p.Ala1236fs)d | NT | NT | NT | 38 | en38 | − | + | |
| 128 | 1 | c.3838C>T (p.Gln1280X)d | + | − | MSH6− | Endometrium | 36 | − | + | + |
| 886 | 1 | c.4001G>A (p.Arg1334Gln) affects ss | + | NT | MSH6nae | Colon NOS | 44 | co61: MSI pos,IHC MSH6 NA | − | + |
S, strategy of molecular testing; MSI, microsatellite instability; Meth, methylation analysis of MLH1 promoter; IHC, immunohistochemical analysis of MLH1, PMS2, MSH2, and MSH6; Tumour tested for MSI, tumour origin or exact location of tumour in case of colon cancer of tumour tested for MSI; Age, age at diagnosis of tumour tested for MSI or age at diagnosis of (first) tumour in case MSI analysis was not performed; Other tumour(s), metachronous or synchronous cancer associated with Lynch syndrome of index patient who had MSI analysis or tumour(s) of index patient who did not have MSI analysis and age at diagnosis; AC, Amsterdam II criteria (Vasen et al, 1999); 2fam, 2 first degree relatives (including index) with cancer associated with Lynch syndrome, one of them with an age at diagnose below 50 years (Rodriguez-Bigas et al, 1997); 1, strategy 1 (germline mutation analysis without preselection by MSI analysis); 2, strategy 2 (first MSI analysis); ss, splice site; +, positive; −, negative; NT, not tested; NA, not assessable; NOS, not otherwise specified; co, colon; en, endometrium; ur, urothelial; ov, ovarian.
Carrier status of patient deduced from mutation status of relatives.
Also carrier of variant c.1A>G (p.Met1?) in MSH2 (paper in preparation).
Also carrier of variant c.965G>A(p.Gly322Asp) in MSH2.
Mutations published elsewhere (Kets et al, 2006).
Adenocarcinoma Caecum of sister with same mutation MSI and IHC MSH6− (1co46 MSI IHC MSH6−).
Also carrier of variant c.65G>C (p.Gly22Ala) in MLH1.