dataset
posted on 2025-07-15, 07:23 authored by Bianca Tesi, Anna Robelius, Berivan Baskin, Vladimir Lazarevic, Stefan Deneberg, Martin Höglund, Linda Fogelstrand, Johanna Ungerstedt, Tatjana Pandzic, Magnus Tobiasson, Hege Gravdahl Garelius, Ekaterina Kuchinskaya, Fredrik Persson, Helena Ågerstam, Helene Hallböök, Thoas Fioretos, Jessika Nordin, Anna Norberg, Ann-Charlotte Thuresson, Sören Lehmann, Claes Ladenvall, Gisela Barbany, Lovisa Vennström, Elisabeth Ejerblad, Lucia Cavelier, Jörg Cammenga, Martin Jädersten, Eva Hellström-Lindberg, Panagiotis Baliakas <p>Supplementary Table 3. Overview of included patients and genetic findings.HGVS=Human Genome Variation Society.</p>
Funding
Swedish Cancer Foundation
Barncancerfonden (Swedish Childhood Cancer Foundation)
Center for Innovative Medicine (CIMED)
Vleugels Stiftelse
Stockholm läns landsting (Stockholm County Council)
Region Uppsala
Svenska Läkaresällskapet (SLS)
Cancerfonden (Swedish Cancer Society)
History
ARTICLE ABSTRACT
In a multicenter prospective cohort study, we assessed the diagnostic yield of the Nordic guidelines for germline investigation in myeloid neoplasms and mapped the spectrum of inherited and somatic variants.
Eighty-five patients (acute myeloid leukemia, n = 38; myelodysplastic syndromes, n = 26; thrombocytopenia, n = 14; and other, n = 7) fulfilling the Nordic criteria for germline investigation, based on (i) medical history or family history suggestive of a germline condition and (ii) relevant findings from the somatic diagnostic work-up (CytoMol), were recruited. The genetic analysis included enhanced whole-exome sequencing (n = 69) or sequencing of specific variants of interest (n = 16).
Pathogenic or likely pathogenic (P/LP) germline variants were identified in 35% of patients (30/85). The diagnostic yield varied from 6% (1/16) in the family history group to 52% (17/33) in the CytoMol group. Germline DDX41 P/LP variants were the most frequent finding (13/30, 43% of all positive cases) almost exclusively found within the CytoMol group (12/13). Seven variants of unknown significance were also detected (TERT n = 2 and DDX41, RTEL1, ETV6, PARN, and SAMD9 n = 1). Five patients carried a P/LP variant in genes associated with another hereditary cancer syndrome (BRCA1 n = 3; PALB2 n = 1; and CHEK2; n = 1). Survival analysis showed a trend for longer survival among patients with acute myeloid leukemia and confirmed or suspected germline predisposition that underwent allogeneic stem cell transplantation.
The implementation of the Nordic guidelines in a prospective Swedish cohort results in a high overall diagnostic yield (35%), proving the feasibility and utility of these or similar guidelines in a clinical setting.
