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Global Proteome Profiling of Anaplastic Large Cell Lymphoma
Author(s) -
Sjostrom Chris,
Seiler Charles,
Crockett David K.,
Tripp Sheryl R.,
ElenitobaJohnson Kojo S. J.,
Lim Megan S.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a220-d
Subject(s) - proteome , western blot , proteomics , cytoplasm , computational biology , tissue microarray , cancer research , immunohistochemistry , microbiology and biotechnology , biology , chemistry , bioinformatics , biochemistry , immunology , gene
Constitutive expression of NPM‐ALK is a key oncogenic event in a subset of ALCL. Global proteomic analysis of NPM‐ALK+ ALCL would facilitate improved understanding of ALCL pathogenesis and the development of novel treatment strategies. Membrane, cytoplasm, and nuclear sub‐cellular fractions of the NPM‐ALK+ SUDHL‐1 cell line were resolved by 1D SDS‐PAGE and analyzed using LC‐MS/MS. The MS data was interpreted using SEQUEST to search the UniProt database, and analyzed by ProteinProphet and INTERACT. A total of 623 proteins consisting of 210 membrane, 229 cytoplasm, and 184 nuclear proteins were identified with a ≤5% error rate. Extensive annotation and PubMed investigation of 209 representative proteins indicated that 19.9% were reported to be expressed in T‐cells and 44.7% were reported to have important function in cancers, while only 2.4% were reported to be involved in ALCL pathogenesis. Categorization of proteins into functional groups was performed using GoMiner. A subset of the identified proteins was confirmed by western blot analysis of NPM‐ALK+ cell lines and immunohistochemistry of ALCL tissue microarrays. This study represents an extensive inventory of the ALCL proteome. In addition, it illustrates the potential for novel pathogenetic discovery in ALCL and the utility of combining cellular sub‐fractionation, 1D SDS‐PAGE, and LC‐MS/MS for comprehensive proteome analysis. This project was supported by the ARUP Institute for Clinical and Experimental Pathology.