Strategy for identification of a potential inherited leukemia predisposition in a 299 patient's cohort with tumor-only sequencing data

Leukemia Research
Almudena Aguilera-DiazMaría José Calasanz

Abstract

Myeloid neoplasms (MN) are usually sporadic late-onset cancers; nevertheless, growing evidence suggests that ∼5% of the cases could emerge as a consequence of inherited predisposition. Distinguishing somatic from germline variants is of vital importance, in order to establish an appropriate individualized management and counsel the patients and their relatives. Since many of the genes associated with myeloid neoplasm germline predisposition (MNGP) are also affected in sporadic MN, we intended to design a strategy to identify potentially inherited variants in a tumor only NGS panel in a cohort of 299 patients with a variety of MN. We considered as indicative of potential inherited origin, variants detected in BM sample at a ∼50% VAF classified as pathogenic, likely pathogenic or of unknown significance detected in MNGP-related genes. A total of 104 suspicious variants from 90 patients were filtered-in in tumor samples. Mutational patterns, follow-up data, and sequencing of a range of non-myeloid tissues were used for narrowing down the list of suspicious variants, and ultimately discriminate their nature. Our data supports the importance of considering variants found upon tumor-only sequencing as potentially of germline origin, ...Continue Reading

References

Mar 14, 2000·Bone Marrow Transplantation·H T GreinixR Knobler
Sep 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas PabstBeatrice U Mueller
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jan 29, 2014·Annals of the New York Academy of Sciences·Allison H WestJane E Churpek
Feb 11, 2015·Best Practice & Research. Clinical Haematology·Daria V Babushok, Monica Bessler
Mar 3, 2015·Bone Marrow Transplantation·C AnthiasB E Shaw
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 8, 2015·Nature Communications·William TapperNicholas C P Cross
Apr 30, 2015·Cancer Cell·Chantana PolprasertJaroslaw P Maciejewski
Jun 9, 2015·Bone Marrow Transplantation·R Peffault de LatourUNKNOWN Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation
Sep 16, 2016·Acta Haematologica·Muhamed BaljevicMartin S Tallman
Dec 4, 2016·Hematology·Wendy Kohlmann, Joshua D Schiffman
Jan 9, 2017·Blood·Claudia Korn, Simón Méndez-Ferrer
Mar 31, 2017·Pathology Oncology Research : POR·Attila Péter KirályCsaba Bödör
Jan 27, 2018·Archives of Pathology & Laboratory Medicine·Juehua GaoYi-Hua Chen
Oct 20, 2018·Blood Advances·Nikola P KonstandinKarsten Spiekermann

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Citations

Jun 9, 2021·Human Molecular Genetics·Simone FeursteinLucy A Godley

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