TP53 Mutation Screening in CLL: NGS Detects Clinically Relevant Subclonal Mutations Missed by Sanger
This review highlights that conventional Sanger sequencing and FISH for del(17p) fail to detect diagnostically relevant TP53 mutations in chronic lymphocytic leukemia, potentially leading to inappropriate treatment decisions. Next-generation sequencing offers superior sensitivity for detecting low-level subclonal TP53 mutations that carry prognostic and therapeutic significance. The authors argue for NGS-based TP53 screening as the standard diagnostic approach in CLL, given the direct impact on treatment selection including chemotherapy avoidance.
The original study
Relevance of TP53 for CLL diagnostics.
- Authors
- Catherwood MA, Gonzalez D, Donaldson D, Clifford R, Mills K, Thornton P
- Journal
- Journal of clinical pathology
- Type
- Journal Article, Review
- PMID
- 30712002
Original abstract
TP53 disruption in chronic lymphocytic leukaemia (CLL) is a well-established prognostic marker and informs on the appropriate course of treatment for patients. TP53 status is commonly assessed by fluorescence in situ hybridisation for del(17 p) and Sanger sequencing for TP53 mutations. At present, current screening methods for TP53 mutations fail to detect diagnostically relevant mutations potentially leading to inappropriate treatment decisions. In addition, low levels of mutations that are proving to be clinically relevant may not be discovered with current less sensitive techniques. This review describes the structure, function and regulation of the TP53 protein, the mutations found in cancer and CLL, the relevance of TP53 disruption in CLL and the current screening methods for TP53 mutations including next-generation sequencing.