Pitfalls in CALR exon 9 mutation detection: A single-center experience in 571 positive patients.
CALR
calreticulin
diagnosis
myeloproliferative neoplasms
Journal
International journal of laboratory hematology
ISSN: 1751-553X
Titre abrégé: Int J Lab Hematol
Pays: England
ID NLM: 101300213
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
13
02
2020
revised:
02
06
2020
accepted:
10
06
2020
pubmed:
3
7
2020
medline:
4
2
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
The pathogenesis of myeloproliferative neoplasms (MPNs) is closely related to the acquisition of specific molecular alterations in JAK2, MPL, or CALR genes, the presence of which represent major diagnostic criteria in the WHO classification. The CALR exon 9 insertions and deletions are very heterogeneous, and their detection mainly relies on polymerase chain reaction (PCR) fragment length analysis. We report on the rare nonclassical profiles that we observed among the 1382 patients analyzed by PCR fragment length analysis. In difficult cases, we tested germline DNA and performed NGS analysis. We faced some troubling results because of the presence of several unexpected peaks. Our investigations showed that they resulted from a mix of isolated or double somatic mutations combined with germline alterations which could be misleading for a correct diagnosis. The precise interpretation of such difficult cases is mandatory as a misinterpretation could lead to the prescription of cytoreductive drugs to nondiseased persons or to an absence of treatment in true MPN patients. Our observations showed that every mutation should be verified by direct Sanger sequencing, and we show that sometimes it may be necessary to study germline DNA and to complement with NGS analysis to precisely interpret the molecular alterations.
Substances chimiques
CALR protein, human
0
Calreticulin
0
Neoplasm Proteins
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
827-832Informations de copyright
© 2020 John Wiley & Sons Ltd.
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