Annotation Detail

Information
Associated Genes
DPYD
Associated Variants
DPYD EXON 11-19 DELETION ( ENST00000370192.8 )
DPYD EXON 11-19 DELETION ( ENST00000370192.8 )
Associated Disease
head and neck squamous cell carcinoma
Source Database
CIViC Evidence
Description
A 69 year old patient diagnosed with HNSCC presented with an unresectable neck mass three months after surgery and adjuvant radiation therapy. A biopsy was taken for whole genome and transcriptome analysis and the patient was started on systemic therapy. After showing resistance to the systemic therapy treatment with 5-FU and leucovorin was initiated based on the discovery of a somatic exon 11-19 in frame deletion in DPYD, which was hypothesized to increase sensitivity to 5-FU in the tumour. A dramatic clinical and radiographic response was sustained for 17 weeks, but following a 3 week treatment break a new nodule appeared. This recurrence showed resistance to re-initiation of treatment with capecitabine (oral 5-FU), and analysis of an additional biopsy provided no evidence as to the mechanism of resistance.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7787
Gene URL
https://civic.genome.wustl.edu/links/genes/1526
Variant URL
https://civic.genome.wustl.edu/links/variants/2893
Rating
4
Evidence Type
Predictive
Disease
Head And Neck Squamous Cell Carcinoma
Evidence Direction
Supports
Drug
Leucovorin,Fluorouracil
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
31871216
Drugs
Drug NameSensitivitySupported
FluorouracilSensitivitytrue
LeucovorinSensitivitytrue