Table 2. MMR gene mutations in rapid autopsy patients.
| Autopsy patient* | Tumour site(s) tested by BROCA targeted sequencing | Mutation burden† (exome) | Hypermutated? | MSI | MMR gene mutation(s)‡ |
|---|---|---|---|---|---|
| 05–165* | Bone, adrenal, liver and lymph node | 855 | Yes | Yes | (1) MSH2-C2orf61 343 kb inversion |
| (2) MSH2-KCNK12 74 kb inversion | |||||
| (3) MSH2-KCNK12 40 kb inversion | |||||
| 03–130 | Lymph node | 647 | Yes | Yes | (1) MSH2 translocation splits the gene t(2;18) |
| (2) MSH2 copy loss | |||||
| (3) MSH6 frameshift (c.2690del) | |||||
| (4) MSH6 copy loss | |||||
| 06–134 | Kidney and lymph node | 314 | Yes | Yes | MLH1 homozygous copy loss |
| 00–010 | Prostate and liver | 673 | Yes | Yes | MSH2 frameshift (c.2364_2365insTACA) |
| 05–123 | Prostate and lymph node | 807 | Yes | Yes | (1) MSH2 frameshift (c.1124_1125insG) |
| (2) MSH2 frameshift (c.1082del) | |||||
| (3) MLH1 frameshift (c.1310del), lymph node only | |||||
| 01–095 | Liver and lymph node | 149 | No | No | None |
| 05–144* | Bone, adrenal, liver and lymph node | 57 | No | No | (1) MSH2 exon 8–16 del |
| (2) MSH6-TESC t(2;12) | |||||
| 05–214 | Bone, liver and lymph node (two sites) | 46 | No | No | None |
| 05–116 | Bone, adrenal, liver and lung | 47 | No | No | None |
| 00–029 | Liver | 37 | No | No | None |
| 00–090 | Lymph node | 69 | No | No | None |
MMR, mismatch repair; MSI, microsatellite instability.
*Fifty total unique autopsy patients were assessed by exome sequencing (see Supplementary Table 1). Listed are a subset of cases that were followed up by targeted deep sequencing for MMR genes. Clinical data for this patient subset is provided in Supplementary Table 6. Patient-matched non-cancer tissue was tested in every case and did not exhibit MSI or MMR mutations. LuCaP 147 and 147CR are derived from autopsy patient 05–165. LuCaP 145.1 and 145.2 are derived from autopsy patient 05–144.
†Number of protein altering somatic mutations by exome sequencing with removing of germline variants from matched-non-tumour samples.
‡Mutations were detected at every tumour site unless otherwise indicated. Mosaic MSH6 frameshift mutations observed in a poly G tract in exon 5 (c.3261dup/del) and poly A tract in exon 7 (c.3573del) were detected in several hypermutated samples and are not included in the table because they are presumed to be due to MSI.