Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next-generation sequencing in Waldenström macroglobulinaemia.
Br J Haematol
; 194(4): 730-733, 2021 08.
Article
in En
| MEDLINE
| ID: mdl-33713429
ABSTRACT
CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non-uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4 (S338X) variant targeted next-generation sequencing (NGS) using unselected bone marrow (BM) samples, and combined allele-specific polymerase chain reaction (AS-PCR) and Sanger sequencing with unselected and CD19-selected BM samples. Our findings showed that targeted NGS frequently yielded false-negative results. Both CD19 selection and AS-PCR markedly improved detection of CXCR4S338X mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Waldenstrom Macroglobulinemia
/
Receptors, CXCR4
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Br J Haematol
Year:
2021
Document type:
Article
Affiliation country: