Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma

Aatur D. Singhi, Siraj M. Ali, Jill Lacy, Andrew Hendifar, Khanh Nguyen, Jamie Koo, Jon H. Chung, Joel Greenbowe, Jeffrey S. Ross, Marina N. Nikiforova, Herbert J. Zeh, Inderpal S. Sarkaria, Anil Dasyam, Nathan Bahary

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Pancrea tic 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.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume15
Issue number5
DOIs
StatePublished - May 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Singhi, A. D., Ali, S. M., Lacy, J., Hendifar, A., Nguyen, K., Koo, J., Chung, J. H., Greenbowe, J., Ross, J. S., Nikiforova, M. N., Zeh, H. J., Sarkaria, I. S., Dasyam, A., & Bahary, N. (2017). Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma. JNCCN Journal of the National Comprehensive Cancer Network, 15(5), 555-562. https://doi.org/10.6004/jnccn.2017.0058