Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (28476735)
Authors Singhi AD, Ali SM, Lacy J, Hendifar A, Nguyen K, Koo J, Chung JH, Greenbowe J, Ross JS, Nikiforova MN, Zeh HJ, Sarkaria IS, Dasyam A, Bahary N
Title Identification of Targetable ALK Rearrangements in Pancreatic Ductal Adenocarcinoma.
Journal Journal of the National Comprehensive Cancer Network : JNCCN
Vol 15
Issue 5
Date 2017 May
URL
Abstract Text 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.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK CDKN2A del FGFR1 T141R SMAD4 Q83* pancreatic ductal adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, a pancreatic ductal adenocarcinoma patient harboring EML4-ALK along with CDKN2A deletion, FGFR1 T141R, SMAD4 Q83*, and a TP53 splice site mutation, experienced disease progression after 2 months of Xalkori (crizotinib) treatment, then received Alecensa (alectinib) and remained on treatment for at least 3 months (PMID: 28476735). 28476735
EML4 - ALK CDKN2A del FGFR1 T141R SMAD4 Q83* pancreatic ductal adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a pancreatic ductal adenocarcinoma patient harboring EML4-ALK along with CDKN2A deletion, FGFR1 T141R, SMAD4 Q83*, and a TP53 splice site mutation, experienced disease progression after 2 months of Xalkori (crizotinib) treatment, then received Alecensa (alectinib) and remained on treatment for at least 3 months (PMID: 28476735). 28476735