Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages

• Verfasst von: Feurstein, Simone [VerfasserIn]
• Verfasst von: Trottier, Amy M. [VerfasserIn]
• Verfasst von: Estrada-Merly, Noel [VerfasserIn]
• Verfasst von: Pozsgai, Matthew [VerfasserIn]
• Verfasst von: McNeely, Kelsey [VerfasserIn]
• Verfasst von: Drazer, Michael W. [VerfasserIn]
• Verfasst von: Ruhle, Brian [VerfasserIn]
• Verfasst von: Sadera, Katharine [VerfasserIn]
• Verfasst von: Koppayi, Ashwin L. [VerfasserIn]
• Verfasst von: Scott, Bart L. [VerfasserIn]
• Verfasst von: Oran, Betul [VerfasserIn]
• Verfasst von: Nishihori, Taiga [VerfasserIn]
• Verfasst von: Agrawal, Vaibhav [VerfasserIn]
• Verfasst von: Saad, Ayman [VerfasserIn]
• Verfasst von: Lindsley, R. Coleman [VerfasserIn]
• Verfasst von: Nakamura, Ryotaro [VerfasserIn]
• Verfasst von: Kim, Soyoung [VerfasserIn]
• Verfasst von: Hu, Zhenhuan [VerfasserIn]
• Verfasst von: Sobecks, Ronald [VerfasserIn]
• Verfasst von: Spellman, Stephen [VerfasserIn]
• Verfasst von: Saber, Wael [VerfasserIn]
• Verfasst von: Godley, Lucy A. [VerfasserIn]
• Titel: Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages
• Verf.angabe: Simone Feurstein, Amy M. Trottier, Noel Estrada-Merly, Matthew Pozsgai, Kelsey McNeely, Michael W. Drazer, Brian Ruhle, Katharine Sadera, Ashwin L. Koppayi, Bart L. Scott, Betul Oran, Taiga Nishihori, Vaibhav Agrawal, Ayman Saad, R. Coleman Lindsley, Ryotaro Nakamura, Soyoung Kim, Zhenhuan Hu, Ronald Sobecks, Stephen Spellman, Wael Saber, and Lucy A. Godley
• E-Jahr: 2022
• Jahr: 18 August 2022
• Umfang: 16 S.
• Fussnoten: Gesehen am 20.03.2023
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2022
• Band/Heft Quelle: 140(2022), 24, Seite 2533-2548
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood.2022015790
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 183959344X

Abstract

Abstract - The frequency of pathogenic/likely pathogenic (P/LP) germ line variants in patients with myelodysplastic syndrome (MDS) diagnosed at age 40 years or less is 15% to 20%. However, there are no comprehensive studies assessing the frequency of such variants across the age spectrum. We performed augmented whole-exome sequencing of peripheral blood samples from 404 patients with MDS and their related donors before allogeneic hematopoietic stem cell transplantation. Single-nucleotide and copy number variants in 233 genes were analyzed and interpreted. Germ line status was established by the presence of a variant in the patient and related donor or for those seen previously only as germ line alleles. We identified P/LP germ line variants in 28 of 404 patients with MDS (7%), present within all age deciles. Patients with P/LP variants were more likely to develop higher-grade MDS than those without (43% vs 25%; P = .04). There was no statistically significant difference in outcome parameters between patients with and without a germ line variant, but the analysis was underpowered. P/LP variants in bone marrow failure syndrome genes were found in 5 patients aged less than 40 years, whereas variants in DDX41 (n = 4), telomere biology disorder genes (n = 2), and general tumor predisposition genes (n = 17) were found in patients aged more than 40 years. If presumed germ line variants were included, the yield of P/LP variants would increase to 11%, and by adding suspicious variants of unknown significance, it would rise further to 12%. The high frequency of P/LP germ line variants in our study supports comprehensive germ line genetic testing for all patients with MDS regardless of their age at diagnosis.