Hybrid Capture-Based Tumor Sequencing and Copy Number Analysis to Confirm Origin of Metachronous Metastases in BRCA1-Mutant Cholangiocarcinoma Harboring a Novel YWHAZ-BRAF Fusion.

We report the case of a patient with a germline BRCA1 mutation who presented with a cholangiocarcinoma driven by the novel YWHAZ-BRAF fusion. Hybrid capture-based DNA sequencing and copy number analysis performed as part of clinical care demonstrated that two later-occurring tumors were clonally derived from the primary cholangiocarcinoma rather than distinct new primaries, revealing an unusual pattern of late metachronous metastasis. We discuss the clinical significance of these genetic alterations and their relevance to therapeutic strategies.
KEY POINTS: Hybrid capture-based next-generation DNA sequencing assays can provide diagnostic clarity in patients with unusual patterns of metastasis and recurrence in which the pathologic diagnosis is ambiguous.To our knowledge, this is the first reported case of a YWHAZ-BRAF fusion in pancreaticobiliary cancer, and a very rare case of cholangiocarcinoma in the setting of a germline BRCA1 mutation.The patient's BRCA1 mutation and YWHAZ-BRAF fusion constitute potential targets for future therapy.
PMID: 29622700 [PubMed - as supplied by publisher]

Source: The Oncologist - April 5, 2018 Category: Cancer & Oncology Authors: Lim HC, Montesion M, Botton T, Collisson EA, Umetsu SE, Behr SC, Gordan JD, Stephens PJ, Kelley RK Tags: Oncologist Source Type: research