FoundationOne Liquid CDx — Clinical Summary

Source (original, already in English): docs_eng/2026_new/FoundationOne_Liquid_CDx_20Aug2026.pdf

Foundation Medicine GmbH (Roche). Next-generation sequencing (NGS) liquid biopsy assay of circulating tumor DNA (ctDNA), testing >300 cancer-related genes.

Report details

Specimen collection date: 20 August 2026 (blood draw)

Report date: 30 August 2026

Ordered test #: ORD-2419716-01

Tumor type: Stomach GIST

Signed by: Tyler Janovitz, MD, PhD

Biomarker findings

Blood Tumor Mutational Burden: 3 Muts/Mb (low)

ctDNA Tumor Fraction: High (32%) — indicates lower risk of false-negative results; genomic findings below are considered reliable.

Microsatellite status: MSI-High not detected

Genomic findings (4 alterations)

KIT — three co-occurring alterations, all likely acquired/secondary resistance mutations:

• exon 11 deletion (Q556_V559>H) — VAF 17.0% — the original driver mutation

• exon 13 V654A — VAF 8.8%. Known secondary resistance mutation to imatinib and avapritinib.

• exon 18 A829P — VAF 4.0% — activation-loop resistance mutation, similar resistance profile to V654A

BRCA2 T3085fs*26 — VAF 1.5%. Possible germline implication flagged by the lab (present in ClinVar as likely pathogenic/pathogenic); follow-up germline testing recommended to distinguish somatic vs. germline. Relevant for PARP-inhibitor sensitivity, not directly GIST-related.

CDKN2A rearrangement, intron 2 — VAF 12.8%. Tumor-suppressor loss; associated with more aggressive disease and shorter survival in GIST, per the report's literature summary.

MTOR A1459D — VAF 0.21% (low-level). Activating mutation; may confer sensitivity to mTOR inhibitors, though clinical relevance in GIST specifically is not established.

Therapy implications — key takeaway

This report explains the clinical resistance already observed: the KIT V654A and A829P secondary mutations are well-documented drivers of resistance to Imatinib, Avapritinib, and Sunitinib — the drugs already tried or being tried on this patient.

Flagged RESISTANT (extensive evidence, in this tumor type):

• Avapritinib — resistance likely (KIT V654A + A829P)

• Imatinib — resistance likely (KIT V654A)

• Sunitinib — resistance likely (KIT V654A)

Therapies with clinical benefit in GIST (this tumor type):

• Regorafenib — NCCN category 1 evidence in GIST; standard third-line option after imatinib/sunitinib failure; multiple Phase 2/3 trials support use, including specifically in patients with KIT exon 11 + secondary mutations.

Unclear resistance:

• Ripretinib — mixed evidence; may still work depending on co-occurring mutation pattern

Therapies with clinical benefit in other tumor types (off-label option in GIST, genomically supported):

• Dasatinib, Nilotinib, Ponatinib, Sorafenib — all have preclinical/clinical evidence of activity against KIT V654A / A-loop resistance mutations specifically, per the report's literature review

Clinical trials

Report lists 3 trials matched to the BRCA2 finding for PARP/ATR inhibitors (NCT05797168, NCT04341181, NCT04817956), located in Germany, UK, Turkey, Denmark, and Norway. 10 additional trials are referenced for KIT findings and 6 for CDKN2A (see full report, pages 15-32, for complete listings).