An oncogenic ALK fusion and an rras mutation in KRAS mutation-negative pancreatic ductal adenocarcinoma

Yoko Shimada, Takashi Kohno, Hideki Ueno, Yoshinori Ino, Hideyuki Hayashi, Takashi Nakaoku, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Kazuaki Shimada, Takuji Okusaka, Nobuyoshi Hiraoka

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Pancreatic adenocarcinoma, Gene fusion Purpose. Oncogenic mutations in the KRAS gene are a wellknown driver event, occurring in >95% of pancreatic cancers. The objective of this study was to identify driver oncogene aberrations in pancreatic cancers without the KRAS mutation. Methods. Whole-exome and transcriptome sequencing was performed on four cases of KRAS mutation-negative pancreatic ductal adenocarcinoma, which were identified in a cohort of 100 cases. Results. One case harbored an oncogenic DCTN1-ALK fusion. The fusion gene enabled interleukin-3-independent growth of Ba/F3 cells and rendered them susceptible to the anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib and alectinib. The structure of the breakpoint junction indicated that the fusion was generated by nonhomologous end joining between a segment of DCTN1 exon DNA and a segment of ALK intron DNA, resulting in the generation of a cryptic splicing site. Another case harbored an oncogenic RRAS mutation that activated the GTPase of the RRAS protein. Conclusion. Rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation.

Original languageEnglish
Pages (from-to)158-164
Number of pages7
JournalOncologist
Volume22
Issue number2
DOIs
Publication statusPublished - 2017 Feb 6
Externally publishedYes

Fingerprint

Adenocarcinoma
Mutation
Gene Fusion
Pancreatic Neoplasms
Exome
Interleukin-3
GTP Phosphohydrolases
DNA
Oncogenes
Transcriptome
Protein-Tyrosine Kinases
Introns
Exons
Carcinogenesis
Growth
Genes
Proteins

Keywords

  • ALK
  • KRAS
  • RRAS

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

An oncogenic ALK fusion and an rras mutation in KRAS mutation-negative pancreatic ductal adenocarcinoma. / Shimada, Yoko; Kohno, Takashi; Ueno, Hideki; Ino, Yoshinori; Hayashi, Hideyuki; Nakaoku, Takashi; Sakamoto, Yasunari; Kondo, Shunsuke; Morizane, Chigusa; Shimada, Kazuaki; Okusaka, Takuji; Hiraoka, Nobuyoshi.

In: Oncologist, Vol. 22, No. 2, 06.02.2017, p. 158-164.

Research output: Contribution to journalArticle

Shimada, Y, Kohno, T, Ueno, H, Ino, Y, Hayashi, H, Nakaoku, T, Sakamoto, Y, Kondo, S, Morizane, C, Shimada, K, Okusaka, T & Hiraoka, N 2017, 'An oncogenic ALK fusion and an rras mutation in KRAS mutation-negative pancreatic ductal adenocarcinoma', Oncologist, vol. 22, no. 2, pp. 158-164. https://doi.org/10.1634/theoncologist.2016-0194
Shimada, Yoko ; Kohno, Takashi ; Ueno, Hideki ; Ino, Yoshinori ; Hayashi, Hideyuki ; Nakaoku, Takashi ; Sakamoto, Yasunari ; Kondo, Shunsuke ; Morizane, Chigusa ; Shimada, Kazuaki ; Okusaka, Takuji ; Hiraoka, Nobuyoshi. / An oncogenic ALK fusion and an rras mutation in KRAS mutation-negative pancreatic ductal adenocarcinoma. In: Oncologist. 2017 ; Vol. 22, No. 2. pp. 158-164.
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