Annotation Detail
Information
- Associated Genes
- PMS2
- Associated Variants
-
PMS2 K706FS*19
PMS2 K706FS*19 - Associated Disease
- glioblastoma
- Source Database
- CIViC Evidence
- Description
- Two siblings (6 and 3.5 years) from nonconsanguineous parents were diagnosed with glioblastoma multiforme. Both tumors harbored TP53 mutations and lack of MGMT promoter hypermethylation as poor prognostic markers. Germline homozygous c.2117delA, p. Lys706SerfsX19 mutation in PMS2, loss of PMS2 staining in the tumor and normal tissue confirmed a diagnosis of biallelic mismatch repair deficiency (bMMRD). Both tumors harbored driver mutations in POLE and were found to harbor 24,680 and 21,919 mutations per exome. Neoantigen load was assessed in 37 bMMRD patients and all malignant tumors had high numbers of predicted neoantigens (7-16x as high as in melanoma, lung or other immunoresponsive cancers). Treatment with nivolumab was begun and both patients had radiologic response. After 9 and 5 months of therapy, respectively, the patient and her brother resumed normal schooling and daily activities.
- Variant Origin
- germline
- Variant Origin
- Rare Germline
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1214
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4371
- Variant URL
- https://civic.genome.wustl.edu/links/variants/508
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Glioblastoma Multiforme
- Evidence Direction
- Supports
- Drug
- Nivolumab
- Evidence Level
- C
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 27001570
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Nivolumab | Sensitivity | true |