Table 1

Cases discussed at UKCGG/CanGene-CanVar Cancer Genetics MDT

Summary: Clinical scenariosConsensus
1. Young patient (age 40–50 years) with MMR-deficient endometrial cancer from an Amsterdam-positive family history (unconfirmed). Germline genetic testing uninformative. Single MSH2 somatic variant detected.Manage as Lynch-like unless further information obtained
2. Deceased proband with MMR-deficient colorectal cancer (isolated loss of PMS2) at 40–50 years. Molecular testing on tissue-derived DNA identified PMS2 pathogenic variant—origin (germline/somatic) could not be determined based on available tissue.Offer germline testing to FDRs for PMS2 variant identified in tumour
3. MMR-deficient (loss of MSH2 and MSH6) endometrial cancer at 50–60 years, keratoacanthoma at 50–60 years. Constitutional testing uninformative. Somatic testing identified two somatic MSH2 variants at low VAF. Cousin with young onset endometrial and rectal cancer also MMR-deficient (loss of MSH2 and MSH6). Somatic testing failed. Amsterdam-positive family history.Manage as Lynch-like unless further information obtained
4. Man with MMR-deficient (loss of MLH1 and PMS2) colorectal at 30–40 years. Mother hysterectomy in late 30s. Brother polyps at 40–50 years. Uninformative constitutional testing.Manage as Lynch-like unless further information obtained
5. MMR-deficient (isolated loss PMS2) pancreatic cancer in a male aged 70–80 years; constitutional testing uninformative, testing on tumour-derived DNA unsuccessful.Colonoscopic screening based on family history
6. MMR-deficient (loss of MLH1 and PMS2) colorectal cancer in 60–70 year old male. Mother ovarian cancer in 80s. No MLH1 promoter hypermethylation or constitutional MMR gene variants identified. Single somatic MLH1 variant identified.National bowel screening
  • FDR, first-degree relative; MDT, multidisciplinary team; MMR, mismatch repair; UKCGG, UK Cancer Genetics Group; VAF, Variant Allele Frequency.