Lynch Syndrome-Associated Mismatch Repair-Deficient Brain Tumor

Case

  • 63/M
  • Diffuse astrocytoma, IDH-wildtype (WHO grade 2)

    • 2 years ago

    • Radiation therapy 59.4 Gy/33 fx

    • Temozolomide (TMZ) treatment, 3 cycle

    • Tumor progression

    • Stereotactic biopsy

Past history

  • Transverse colon cancer, 17 years ago and 10 year ago
    • MSH2 loss of nuclear staining
  • Infiltrating urothelial carcinoma of bladder, 4 years ago
  • Squamous cell carcinoma of skin, this year
  • Sebaceoma
    • Muir Torre (myoor-TOR-ay) variant of Lynch syndrome

Family history

  • Absent

Pathology

  • ATRX loss (-)
  • 1p19q codeletion (-)
  • MGMT methylation (-)
  • TERT promoter mutation (-)

NGS

Hugo_Symbol Variant_Classification HGVSc HGVSp_Short
ARID2 Frame_Shift_Del c.4086_4087del p.C1362*
ZFHX3 Frame_Shift_Del c.9590_9591delinsC p.Q3197Pfs*44
ZFHX3 Frame_Shift_Del c.6591_6592del p.F2198Qfs*6
PDGFRA In_Frame_Del c.2529_2531del p.I843del
PIK3CA Missense_Mutation c.323G>A p.R108H
PIK3CA Missense_Mutation c.1030G>A p.V344M
TP53 Missense_Mutation c.818G>A p.R273H
MSH2 Nonsense_Mutation c.1418C>G p.S473*
SETD2 Nonsense_Mutation c.1366C>T p.R456*
SETD2 Nonsense_Mutation c.208C>T p.R70*
CDKN2A Nonsense_Mutation c.172C>T p.R58*
KMT2A Nonsense_Mutation c.1822C>T p.R608*
ARID2 Nonsense_Mutation c.4926G>A p.W1642*
FANCM Nonsense_Mutation c.1717C>T p.R573*

MSI (NGS)

  • MSI Status: MSS
  • MSI Score: 13.87

Tumor mutation burden

  • 22.69 (Mutations/Mb)

Temozolomide (TMZ) treatment

Temozolomide (TMZ) treatment

Temozolomide (TMZ) treatment

This case

Summary

  • Brain tumor, hypermutated

    • Temozolomide-treated hypermutated tumors, recurrent

      • MGMT promoter methylation

      • Aquired MMR-d

    • Lynch Syndrome-Associated Mismatch Repair-Deficient Brain Tumor