Skip to main content

Table 2 Overview of somatic mutation count by tumor type and by observed MMR IHC

From: A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome

SLS tumors testeda

Number of somatic MMR mutations

CRC (n = 61)

EC (n = 22)

SST (n = 22)

Total (n = 105 tumors)g

Overall

Double somatic MMR mutations (dMMR-DS)b

55 (90.2%)f

15 (68.2%)

17 (77.3%)

87 (82.9%)

Single somatic MMR mutation (dMMR-SS)c

3 (4.9%)

4 (18.2%)

3 (13.6%)

10 (9.5%)

No somatic MMR mutations (dMMR-SLS)d

3 (4.9%)

3 (13.6%)

2 (9.1%)

8 (7.6%)

Pattern of MMR IHC losse

MLH1/PMS2

Double somatic mutations in MLH1

27 (93.1%)

7 (70%)

4 (66.7%)

38 (84.4%)

Single somatic mutation in MLH1

1 (3.4%)

1 (10%)

1 (16.7%)

3 (6.7%)

No somatic mutation in MLH1

1 (3.4%)

2 (20%)

1 (16.7%)

4 (8.9%)

Total

29 (100%)

10 (100%)

6 (100%)

45 (100%)

MSH2/MSH6

Double somatic mutations in MSH2

23 (85.2%)

3 (60%)

12 (80%)

38 (80.9%)

Single somatic mutation in MSH2

2 (7.4%)

2 (40%)

2 (13.3%)

6 (12.8%)

No somatic mutation in MSH2

2 (7.4%)

0 (0%)

1 (6.7%)

3 (6.4%)

Total

27 (100%)

5 (100%)

15 (100%)

47 (100%)

MSH6

Double somatic mutations in MSH6

4 (100%)

5 (71.4%)

1 (100%)

10 (83.3%)

Single somatic mutation in MSH6

0 (0%)

1 (14.3%)

0 (0%)

1 (8.3%)

No somatic mutation in MSH6

0 (0%)

1 (14.3%)

0 (0%)

1 (8.3%)

Total

4 (100%)

7 (100%)

1 (100%)

12 (100%)

PMS2

Double somatic mutations in PMS2

1 (100%)

0 (0%)

0 (0%)

1 (100%)

Single somatic mutation in PMS2

0 (0%)

0 (0%)

0 (0%)

0 (0%)

No somatic mutation in PMS2

0 (0%)

0 (0%)

0 (0%)

0 (0%)

Total

1 (100%)

0 (0%)

0 (0%)

1 (100%)

  1. CRC colorectal cancer, EC endometrial cancer, SST sebaceous skin tumor, IHC immunohistochemistry, MMR DNA mismatch repair, SLS suspected Lynch syndrome, dMMR-DS DNA mismatch repair deficient tumor with double somatic mutations, dMMR-SS DNA mismatch repair deficient tumor with single somatic mutation, dMMR-SLS DNA mismatch repair deficient tumor with no somatic mutations. Numbers in bold indicate the number of double somatic cases (the most common sporadic subtype) by MMR gene
  2. aFor assessment of the presence of somatic mutations fitting to MMR IHC loss, one tumor presenting with loss of all four MMR proteins (SLS272) harboring biallelic MLH1 and biallelic MSH6 mutations was excluded from findings presented in Table 2
  3. bDouble somatic MMR mutations describes the presence of two or more somatic mutations in the same MMR gene where the pattern of protein loss by IHC indicates that same gene e.g. two MSH2 somatic mutations in a tumor showing loss of MSH2/MSH6 expression
  4. cSingle somatic MMR mutation describes the presence of only one somatic mutation in the same MMR gene where the pattern of protein loss by IHC indicates that same gene e.g. single MSH2 somatic mutation in a tumor showing loss of MSH2/MSH6 expression
  5. dNo somatic MMR mutations describes the absence of any somatic mutations in the same MMR gene where the pattern of protein loss by IHC indicates a defective gene e.g., no somatic mutations observed in MSH2 in a tumor showing loss of MSH2/MSH6 expression by IHC
  6. eThe updated pattern of MMR IHC loss from internal MMR IHC testing was used in this table
  7. fOne CRC tumor (SLS272) showed loss of all four MMR proteins by IHC and had double somatic MLH1 mutations and double somatic MSH6 mutations was not included in this table
  8. gThese 105 SLS tumors excluded tumors re-categorized as dMMR-LS, dMMR-MLH1me, dMMR-PriEpi and pMMR by re-testing MLH1 methylation, MMR IHC and deriving dMMR status from panel sequencing and identification of germline MMR pathogenic variants
Back to article page

Journal of Translational Medicine

ISSN: 1479-5876

Contact us