Table 4

NGS somatic analysis on CRC and EC with IHC loss

IHC lossNumberHypermethylationGermline from tumourGermline negative bloodSomaticNo cause foundCause of IHC loss found
Colorectal somatic testing
 MLH1/PMS2470/464 MLH1*4330 MLH11334/47 (72%)
10/34 monoallelic
 MSH2/MSH638nt4
2 MSH6
2 MSH2
3427
8 MSH6
19 MSH2
731/38 (82%)
10/38 monoallelic
Endometrial somatic testing
 MLH1/PMS250/5054 MLH114/5 (80%)
3/5 double somatic†
 MSH2/MSH613nt0137 MSH6
6 MSH2
013/13 (100%)
10/13 double somatic
  • For CRC: 13 MLH1 loss no cause found 2/3 MSH−1 double somatic PTEN, 1 POLD1.

  • 7 MSH2 loss no cause found 4/5 MSS? Overcall: 1 MSH double somatic PTEN.

  • *One mosaic low level 16% VAF missed on germline testing found after tumour somatic c.1975C>T p.(Arg659Ter) MLH1.

  • †Most samples with monoallelic variants had allele frequencies of <10%, which precludes LOH analysis.

  • CRC, colorectal cancer; EC, endometrial cancer; IHC, immunohistochemistry; LOH, loss of heterozygosity; NGS, next-generation sequencing; VAF, variant allele frequency.