Table 1

Patients groups and results

GroupI) CEMII) H1DIII) CIMPIV) LSV) C-H1PControl C-nLS
Number of patients1637102832421150
MSIMSI-HMSI-HMSI-HMSI-H106 MSI-H/136 MSSn.a.
IHC MLH1neg.neg.neg.neg.pos.n.a.
MLH1 germline variantneg.neg.neg.pos.183 neg./59 n.a.n.a.
MLH1 CEMpos. 50%neg.neg.neg.106 neg./136 n.a.n.a.
MLH1 tumour methylationpos. 50%neg.pos.neg.n.a.n.a.
BRAF mutationneg.neg.pos. neg.neg./n.a.n.a.n.a.
CRCYesYesYesYesYesNo
Rare MLH1 promoter variants2 (12.5%):
c.-63_-58delins18;
c.-269C>G
3 (8.1%):
c.-42C>T;
c.-269C>G;
c.-477T>C
2 (2%):
c.-269C>G;
c.-369A>G
1 (1.2%):
c.-33T>G
8 (7.6%):
c.[-28A>G;-7C>T];
c.-28A>G;
c.-230G>C;
c.-269C>G 4x;
c.-593G>C
3 (0.3%):
c.[-28A>G;-7C>T] 2x;
c.-269C>G
  • Categorisation of 1630 patients into different groups by molecular characteristics including the status of microsatellite instability (MSI), immunohistochemical staining (IHC) of MLH1 in the tumour (positive: pos., negative: neg.), MLH1 germline variants, methylation of the MLH1 promoter in blood (CEM) and in tumour, BRAF mutation status in NM_004333.4 c.1799T>A p.Val600Glu in the tumour and diagnosis of colorectal cancer (CRC). Not analysed: n.a. 480 patients with CRC were subdivided into groups I–V, of those, I–IV had MLH1-deficient tumours of different causes: I) constitutional MLH1 epimutation (CEM), II) unsolved MLH1-deficiency in the tumour (H1D), III) CIMP tumours, IV) patients with Lynch syndrome (LS) with pathogenic MLH1 germline variants (class 4 or 5 according to InSiGHT). Group V consists of 242 patients with MLH1-proficient tumours (C-H1P) and served as a control group. The second control group (C-nLS) comprises patients with tumours indicating other syndromes, but not LS. The number of rare promoter variants detected in each group (and their percentage in brackets) is given and variant nomenclature is provided in relation to the MLH1 translation start.