Beyond myeloid neoplasms germline guidelines : Validation of the thresholds criteria in the search of germline predisposition variants
Mestre, Julia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Chaparro, Lorea (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Manzanares Mileo, Ana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Xicoy, Blanca (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Zamora, Lurdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sole, F (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Calvete, Oriol (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Germline predisposition to myeloid neoplasms can be suspected in patients younger than 50 years or when harboring mutations with a variant allele frequency (VAF) higher than 30% for point mutations in specific genes. To investigate the VAF thresholds' accuracy we have explored the prevalence of germline variants below the 30% VAF threshold. A total of 40 variants with VAF lower than 30% in bone marrow samples of myeloid neoplasm patients were selected and studied in CD3 + cells. All the selected variants were not found in CD3 + cells except one variant in the SF3B1 gene. However, the whole series was found somatic. Selected variants were also evaluated with our previously studied series of 52 variants with VAF higher than 30%. Our study suggests that variants with VAF below 30% are strong somatic candidates but the variants with VAF higher than 30% cannot be considered of germline origin.
Grants:	Instituto de Salud Carlos III PI23/00007 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-560
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Germline guidelines ; Germline predisposition ; Myelodysplastic syndromes (MDS) ; Variant allele frequency (VAF)
Published in:	EJHaem, Vol. 5 (october 2024) , p. 1021-1027, ISSN 2688-6146

DOI: 10.1002/jha2.1012
PMID: 39415912

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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