Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses.
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Authors
Ng, Pei Sze
Pan, Jia Wern
Ahmad Zabidi, Muhammad Mamduh
Rajadurai, Pathmanathan
Yip, Cheng Har
Publication Date
2021-04-23Journal Title
NPJ Breast Cancer
ISSN
2374-4677
Publisher
Springer Science and Business Media LLC
Volume
7
Issue
1
Pages
46
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Ng, P. S., Pan, J. W., Ahmad Zabidi, M. M., Rajadurai, P., Yip, C. H., Reuda, O. M., Dunning, A., et al. (2021). Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses.. NPJ Breast Cancer, 7 (1), 46. https://doi.org/10.1038/s41523-021-00254-4
Abstract
Rare protein-truncating variants (PTVs) in PALB2 confer increased risk to breast cancer, but relatively few studies have reported the characteristics of tumours with PALB2 PTVs. In this study, we describe molecular characteristics of tumours with either germline or somatic alterations in PALB2. DNA from fresh frozen tumour tissues and matched peripheral blood lymphocytes for 560 breast cancer patients was subjected for whole-exome sequencing (WES), and RNA from tumour tissues was subjected to RNA sequencing (RNA-seq). We found six cases with germline and three with somatic protein-truncating variants in PALB2. The characteristics of tumours in patients with PALB2 PTVs were similar to those with BRCA1 and BRCA2 PTVs, having significantly more somatic alterations, and a high proportion of the mutational signature and genomic scar scores characteristic of deficiencies in homologous recombination (HR), compared to tumours arising in non-carriers. Unlike tumours arising in patients with BRCA1 and BRCA2 PTVs, PALB2 tumours did not have high prevalence of TP53 somatic alterations or an enriched immune microenvironment. In summary, PALB2 tumours show the homologous recombination deficiencies characteristic of BRCA1 and BRCA2 tumours, and highlight the potential clinical relevance of PALB2 mutational status in guiding therapeutic choices.
Sponsorship
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
Medical Research Council (MR/P012442/1)
Cancer Research UK (A16942)
Wellcome Trust (203477/Z/16/Z)
Medical Research Council (MR/P012930/1)
Identifiers
External DOI: https://doi.org/10.1038/s41523-021-00254-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/322361
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