PMC9379095_01
Timeline of the disease history and management. TMZ, Temozolomide.
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As illustrated in Figure 1, he received a craniotomy with tumor resection about thirty-six years ago.
Diagnosis of an oligodendroglioma, IDH-mutant and 1p/19q co-deleted, CNS WHO grade 3 by (A) MRI before the most recent tumor resection; (B) H&E staining (20X) and (C) DNA methylation profiling of the tumor sample from the most recent tumor resection.
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Approximately ten years later, the MRI findings were suggestive of disease progression (Figure 2A). Pathology demonstrated oligodendroglioma, IDH-mutant and 1p/19q-codeleted, CNS WHO grade 3 (Figure 2B). DNA methylation profiling was consistent with the diagnosis of oligodendroglioma, IDH-mutant and 1p/19q-codeleted (Figure 2C).
(A)
PMS2 mutation found in the proband (c.251-2A>T); (B) Immunohistochemistry staining of MMR proteins, including MLH1, MSH6, MSH2, and PMS2 (20X) using the tumor sample from the most recent tumor resection.
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Tumor/Normal Whole Exome Sequencing (T/N WES; NCI-COMPASS-NIH) revealed that he carries a pathogenic germline mutation in PMS2 (c.251-2A>T splice variant) (Figure 3A). This splice alteration affects a canonical splice acceptor at nucleotide position -2, upstream of coding exon 4 in PMS2. Despite the germline PMS2 mutation, it did not cause a complete loss of PMS2 protein expression, and all MMR proteins were positively expressed (Figure 3B).
Three-generation family history pedigree.
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While his family history is less characteristic of LS, he has a brother with colon cancer (Figure 4).