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Title: A practical guide for mutational signature analysis in hematological malignancies
Author: Maura, Francesco
Degasperi, Andrea
Nadeu, Ferran
Leongamornlert, Daniel
Davies, Helen
Moore, Luiza
Royo, Romina
Ziccheddu, Bachisio
Puente, Xose S.
Avet-Loiseau, Hervé
Campbell, Peter J.
Nik-Zainal, Serena
Campo Güerri, Elias
Munshi, Nikhil
Bolli, Niccolò
Keywords: Leucèmia mieloide
Mutació (Biologia)
Myeloid leukemia
Mutation (Biology)
Issue Date: 5-Jul-2019
Publisher: Nature Publishing Group
Abstract: Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2019, vol. 10, p. 2969
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)

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