Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses

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 PA...

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Autores principales:	Pei Sze Ng, Jia Wern Pan, Muhammad Mamduh Ahmad Zabidi, Pathmanathan Rajadurai, Cheng Har Yip, Oscar M. Reuda, Alison M. Dunning, Antonis C. Antoniou, Douglas F. Easton, Carlos Caldas, Suet-Feung Chin, Soo Hwang Teo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0aad972192044d50993ee44394768c43
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spelling	oai:doaj.org-article:0aad972192044d50993ee44394768c432021-12-02T18:28:34ZCharacterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses10.1038/s41523-021-00254-42374-4677https://doaj.org/article/0aad972192044d50993ee44394768c432021-04-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00254-4https://doaj.org/toc/2374-4677Abstract 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.Pei Sze NgJia Wern PanMuhammad Mamduh Ahmad ZabidiPathmanathan RajaduraiCheng Har YipOscar M. ReudaAlison M. DunningAntonis C. AntoniouDouglas F. EastonCarlos CaldasSuet-Feung ChinSoo Hwang TeoNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Pei Sze Ng Jia Wern Pan Muhammad Mamduh Ahmad Zabidi Pathmanathan Rajadurai Cheng Har Yip Oscar M. Reuda Alison M. Dunning Antonis C. Antoniou Douglas F. Easton Carlos Caldas Suet-Feung Chin Soo Hwang Teo Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
description	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.
format	article
author	Pei Sze Ng Jia Wern Pan Muhammad Mamduh Ahmad Zabidi Pathmanathan Rajadurai Cheng Har Yip Oscar M. Reuda Alison M. Dunning Antonis C. Antoniou Douglas F. Easton Carlos Caldas Suet-Feung Chin Soo Hwang Teo
author_facet	Pei Sze Ng Jia Wern Pan Muhammad Mamduh Ahmad Zabidi Pathmanathan Rajadurai Cheng Har Yip Oscar M. Reuda Alison M. Dunning Antonis C. Antoniou Douglas F. Easton Carlos Caldas Suet-Feung Chin Soo Hwang Teo
author_sort	Pei Sze Ng
title	Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
title_short	Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
title_full	Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
title_fullStr	Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
title_full_unstemmed	Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
title_sort	characterisation of palb2 tumours through whole-exome and whole-transcriptomic analyses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0aad972192044d50993ee44394768c43
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Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses

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