Open AccessHybrid Capture‐Based Tumor Sequencing and Copy Number Analysis to Confirm Origin of Metachronous Metastases in BRCA1‐ Mutant Cholangiocarcinoma Harboring a Novel YWHAZ‐BRAF Fusion
Author(s) -
Lim Huat C.,
Montesion Meagan,
Botton Thomas,
Collisson Eric A.,
Umetsu Sarah E.,
Behr Spencer C.,
Gordan John D.,
Stephens Phil J.,
Kelley Robin K.
Publication year - 2018
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2017-0645
Subject(s) - medicine , metastasis , cancer , mutation , fusion gene , germline mutation , targeted therapy , dna sequencing , cancer research , clinical significance , germline , bioinformatics , biology , pathology , genetics , gene
Biliary tract cancers such as cholangiocarcinoma represent a heterogeneous group of cancers that can be difficult to diagnose. Recent comprehensive genomic analyses in large cholangiocarcinoma cohorts have defined important molecular subgroups within cholangiocarcinoma that may relate to anatomic location and etiology [1][Farshidfar F, 2017], [2][Jusakul A, 2017], [3][Lee H, 2016], [4][Zhu AX, 2014] and may predict responsiveness to targeted therapies in development [5][Javle M, 2016], [6][Borad MJ, 2014], [7][Borger DR, 2012]. These emerging data highlight the potential for tumor genomics to inform diagnosis and treatment options in this challenging tumor type. 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.