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Aberrant expression of glycosylation in juvenile gastrointestinal stromal tumors
Author(s) -
Takahashi Tsuyoshi,
Naka Tetsuji,
Fujimoto Minoru,
Serada Satoshi,
Horino Jirou,
Terabe Fumitaka,
Hirota Seiichi,
Miyoshi. Eiji,
Hirai Toshihiro,
Nakajima Kiyokazu,
Nishitani Akiko,
Souma Yoshihito,
Sawa Yoshiki,
Nishida Toshirou
Publication year - 2008
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200700119
Subject(s) - gist , juvenile , pdgfra , biology , stromal cell , immunostaining , glycan , mutation , cancer research , medicine , microbiology and biotechnology , gene , genetics , immunohistochemistry , immunology , glycoprotein
Most adult gastrointestinal stromal tumors (GIST) are thought to be caused by activating mutations in the KIT or PDGFRA gene. However, many juvenile GIST lack either mutation and are considered to develop with a different pathogenesis. To investigate the molecular characteristics of juvenile GIST, we analyzed the proteome difference in phosphorylated protein between adult and juvenile GIST. Eleven GIST samples (seven adult cases and four juvenile cases lacking either mutation) were analyzed by using immunostaining and LC‐MS/MS. Comparative analysis of tyrosine‐phosphorylated protein levels showed that juvenile GIST possessed phosphorylated KIT in spite of lacking mutation in the KIT gene. Moreover, downstream signals of KIT were also activated as in adult GIST. Although, SDS‐PAGE gels showed that there was a difference of each KIT bands between adult and juvenile GIST, they became the same after removal of N‐glycans or sialic acids. Moreover, one of the most typical enzymes, ST6Gal1, which transfers Neu5Ac residues in α2‐6 linkage to Gal β1‐4GlcNAc units on N‐glycans, is significantly less expressed in juvenile GIST. This suggests that the difference in KIT is generated by post‐translational modification and may play a role in the progression of juvenile GIST.