Seeing the smoking gun: a sensitive and specific method to visualize loss of the tumour suppressor, fumarate hydratase, in human tissues

PH Maxwell - The Journal of Pathology, 2011 - Wiley Online Library
The Journal of Pathology, 2011Wiley Online Library
In this issue of the Journal of Pathology, Bardella et al report a method for identifying
tumours that lack fumarate hydratase. The approach they use is immunodetection of proteins
that have been modified by a non‐enzymatic reaction of thiol groups in proteins with
fumarate, which is termed succination. Validation included the use of mice with targeted
inactivation of fumarate hydratase in the kidney, extensive studies of normal human tissues
and examination of over 1000 specimens from human cancers not associated with FH …
Abstract
In this issue of the Journal of Pathology, Bardella et al report a method for identifying tumours that lack fumarate hydratase. The approach they use is immunodetection of proteins that have been modified by a non‐enzymatic reaction of thiol groups in proteins with fumarate, which is termed succination. Validation included the use of mice with targeted inactivation of fumarate hydratase in the kidney, extensive studies of normal human tissues and examination of over 1000 specimens from human cancers not associated with FH mutations. Detection of protein succination is likely to provide a sensitive and specific method for pathologists to identify the small proportion of papillary renal cell carcinomas that are associated with germline mutations in the FH gene. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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