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J Natl Compr Canc Netw. 2017 May;15(5):555-562.

Identification of Targetable ALK Rearrangements in Pancreatic Ductal Adenocarcinoma.

Author information

1
From Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Foundation Medicine, Inc, Cambridge, Massachusetts; Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut; Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Pathology, Albany Medical Center, Albany, New York; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with ALK-rearranged tumors. However, ALK translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0.16%) that harbored an ALK fusion gene: an exon 6 EML4-exon 20 ALK translocation (n=3), an exon 13 EML4-exon 20 ALK translocation (n=1), and an exon 3 STRN-exon 20 ALK translocation (n=1). Among the most prevalent PDAC-related genes, activating KRAS mutations were absent in all 5 cases, who were <50 years of age. Among patients aged <50 years in our study cohort, ALK translocations constituted 1.3% of PDACs. Four of 5 patients were treated with an ALK inhibitor, and 3 of these patients demonstrated stable disease, radiographic response, and/or normalization of serum CA 19-9. Although rare, ALK fusions occur in PDAC, and screening for ALK rearrangements should be considered in young patients with PDAC.

PMID:
28476735
[Indexed for MEDLINE]

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