From:  Colon cancer in a patient with a mosaic monoallelic germline pathogenic NF1 gene variant

 Summary of diagnostic tests, verified results, and clinical interpretation.

Test categoryVerified resultInterpretation
Germline multigene panel (saliva)Mosaic monoallelic pathogenic NF1 variant NM_000267.3:c.1756_1759del (p.Thr586Valfs*18); variant allele frequency (VAF) ~35%; no pathogenic Lynch syndrome-associated germline variant detectedSupports post-zygotic mosaic NF1 and argues against an inherited mismatch repair syndrome identified on the germline panel
Biopsy pathologyAdenocarcinomaEstablished malignant epithelial tumor of colonic origin
Mismatch repair immunohistochemistryIsolated loss of postmeiotic segregation increased 2 (PMS2); retained mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), and mutS homolog 6 (MSH6)Pattern consistent with mismatch repair deficiency; prompted molecular characterization and Lynch syndrome consideration
Baseline imagingNo metastatic disease identifiedSupported localized disease at diagnosis
Surgical pathologyTwo foci of invasive adenocarcinoma (3.5 cm and 4.0 cm) in the ascending colon, well differentiated with mucinous features; T3 N0 and T2 N0Localized stage II colon adenocarcinoma. T3 N0 indicates tumor extension through the muscularis propria into pericolonic tissues without regional nodal metastasis; T2 N0 indicates invasion into, but not through, the muscularis propria without nodal metastasis
Tumor next-generation sequencingMicrosatellite instability-high (MSI-H); tumor mutational burden 43 mutations/Mb; no somatic BRAF or NF1 alteration detectedHypermutated dMMR tumor profile with no detected somatic BRAF driver or second somatic NF1 event in available testing
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dMMR: deficient mismatch repair; NF1: neurofibromatosis type 1.