Open AccessIdentification of candidates for driver oncogenes in scirrhous‐type gastric cancer cell lines
Author(s) -
Sai Eirin,
Miwa Yoshiyuki,
Takeyama Reina,
Kojima Shinya,
Ueno Toshihide,
Yashiro Masakazu,
Seto Yasuyuki,
Mano Hiroyuki
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14111
Subject(s) - biology , gene , somatic cell , transmembrane protein , cancer research , fusion gene , exome , cell culture , cancer , cancer cell , cell type , mutation , exome sequencing , genetics , cell , receptor
Scirrhous‐type gastric cancer ( SGC ) is one of the most intractable cancer subtypes in humans, and its therapeutic targets have been rarely identified to date. Exploration of somatic mutations in the SGC genome with the next‐generation sequencers has been hampered by markedly increased fibrous tissues. Thus, SGC cell lines may be useful resources for searching for novel oncogenes. Here we have conducted whole exome sequencing and RNA sequencing on 2 SGC cell lines, OCUM ‐8 and OCUM ‐9. Interestingly, most of the mutations thus identified have not been reported. In OCUM ‐8 cells, a novel CD 44‐ IGF 1R fusion gene is discovered, the protein product of which ligates the amino‐terminus of CD 44 to the transmembrane and tyrosine‐kinase domains of IGF 1R. Furthermore, both CD 44 and IGF 1R are markedly amplified in the OCUM ‐8 genome and abundantly expressed. CD 44‐ IGF 1R has a transforming ability, and the suppression of its kinase activity leads to rapid cell death of OCUM ‐8. To the best of our knowledge, this is the first report describing the transforming activity of IGF 1R fusion genes. However, OCUM ‐9 seems to possess multiple oncogenic events in its genome. In particular, a novel BORCS 5‐ ETV 6 fusion gene is identified in the OCUM ‐9 genome. BORCS 5‐ ETV 6 possesses oncogenic activity, and suppression of its message partially inhibits cell growth. Prevalence of these novel fusion genes among SGC awaits further investigation, but we validate the significance of cell lines as appropriate reagents for detailed genomic analyses of SGC .