Journal Article

Oncogenic <i>MAP2K1</i> mutations in human epithelial tumors

Young Lim Choi, Manabu Soda, Toshihide Ueno, Toru Hamada, Hidenori Haruta, Azusa Yamato, Kazutaka Fukumura, Mizuo Ando, Masahito Kawazu, Yoshihiro Yamashita and Hiroyuki Mano

in Carcinogenesis

Volume 33, issue 5, pages 956-961
Published in print May 2012 | ISSN: 0143-3334
Published online February 2012 | e-ISSN: 1460-2180 | DOI:
Oncogenic MAP2K1 mutations in human epithelial tumors

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics


Show Summary Details


The scirrhous subtype of gastric cancer is a highly infiltrative tumor with a poor outcome. To identify a transforming gene in this intractable disorder, we constructed a retroviral complementary DNA (cDNA) expression library from a cell line (OCUM-1) of scirrhous gastric cancer. A focus formation assay with the library and mouse 3T3 fibroblasts led to the discovery of a transforming cDNA, encoding for MAP2K1 with a glutamine-to-proline substitution at amino acid position 56. Interestingly, treatment with a MAP2K1-specific inhibitor clearly induced cell death of OCUM-1 but not of other two cells lines of scirrhous gastric cancer that do not carry MAP2K1 mutations, revealing the essential role of MAP2K1(Q56P) in the transformation mechanism of OCUM-1 cells. By using a next-generation sequencer, we further conducted deep sequencing of the MAP2K1 cDNA among 171 human cancer specimens or cell lines, resulting in the identification of one known (D67N) and four novel (R47Q, R49L, I204T and P306H) mutations within MAP2K1. The latter four changes were further shown to confer transforming potential to MAP2K1. In our experiments, a total of six (3.5%) activating mutations in MAP2K1 were thus identified among 172 of specimens or cell lines for human epithelial tumors. Given the addiction of cancer cells to the elevated MAP2K1 activity for proliferation, human cancers with such MAP2K1 mutations are suitable targets for the treatment with MAP2K1 inhibitors.

Journal Article.  3784 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.