Abstract:
:The large number of mutations identified across all cancers represents an untapped reservoir of targets that can be useful for therapeutic targeting if highly selective, mutation-specific reagents are available. We report here our attempt to generate such reagents: monoclonal antibodies against the most common R175H, R248Q, and R273H hotspot mutants of the tumor suppressor p53. These antibodies recognize their intended specific alterations without any cross-reactivity against wild-type (WT) p53 or other p53 mutants, including at the same position (as exemplified by anti-R248Q antibody, which does not recognize the R248W mutation), evaluated by direct immunoblotting, immunoprecipitation, and immunofluorescence methods on transfected and endogenous proteins. Moreover, their clinical utility to diagnose the presence of specific p53 mutants in human tumor microarrays by immunohistochemistry is also shown. Together, the data demonstrate that antibodies against specific single-amino-acid alterations can be generated reproducibly and highlight their utility, which could potentially be extended to therapeutic settings.
journal_name
Cell Repjournal_title
Cell reportsauthors
Hwang LA,Phang BH,Liew OW,Iqbal J,Koh XH,Koh XY,Othman R,Xue Y,Richards AM,Lane DP,Sabapathy Kdoi
10.1016/j.celrep.2017.11.112subject
Has Abstractpub_date
2018-01-02 00:00:00pages
299-312issue
1issn
2211-1247pii
S2211-1247(17)31796-5journal_volume
22pub_type
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