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Eur Urol. 2019 Jan;75(1):11-15. doi: 10.1016/j.eururo.2018.08.026. Epub 2018 Sep 21.

Mutational Profile of Aggressive, Localised Prostate Cancer from African Caribbean Men Versus European Ancestry Men.

Author information

1
Synergie Lyon Cancer, Plateforme de Bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France.
2
CeRePP, Paris, France; CHU de Poitiers, Hôpital de la Miletrie, Poitiers, France; CHRU de Tours, Department of Pathology, Tours, France.
3
Centre Léon Bérard, Département de Recherche Translationnelle et de l'Innovation, Génomique des Cancers, Lyon, France.
4
Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France.
5
CHU de Poitiers, Hôpital de la Miletrie, Poitiers, France.
6
Inserm U1085 - IRSET, Pointe à Pitre, Guadeloupe.
7
CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
8
Inserm U1085 - IRSET, Pointe à Pitre, Guadeloupe; CHU Pointe-à-Pitre/Abymes, Department of Urology, Pointe à Pitre, Guadeloupe.
9
CeRePP, Paris, France; Sorbonne Université, GRC n(∘)5, ONCOTYPE-URO, Paris, France.
10
Synergie Lyon Cancer, Plateforme de Bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France; INRIA, Montbonnot-Saint Martin, France.
11
CeRePP, Paris, France; Sorbonne Université, GRC n(∘)5, ONCOTYPE-URO, Paris, France; Assistance Publique Hôpitaux de Paris, Department of Urology, Academic Hospital Paris Est, Paris, France. Electronic address: olivier.cussenot@aphp.fr.

Abstract

Causes of high mortality of prostate cancer in men of African ancestry living in the French West Indies are still debated, between suspicions of environmental factors and genetic susceptibility. We report an integrated genomic study of 25 tumour tissues from radical prostatectomy of aggressive (defined by International Society of Urological Pathology ≥3) prostate cancer patients (10 African Caribbean and 15 French Caucasian) using single nucleotide polymorphism arrays, whole-genome sequencing, and RNA sequencing. The results show that African Caribbean tumours are characterised by a more frequent deletion at 1q41-43 encompassing the DNA repair gene PARP1, and a higher proportion of intrachromosomal rearrangements including duplications associated with CDK12 truncating mutations. Transcriptome analyses show an overexpression of genes related to androgen receptor activity in African Caribbean tumours, and of PVT1, a long non-coding RNA located at 8q24 that confirms the strong involvement of this region in prostate tumours from men of African ancestry. Patient summary: Mortality of prostate cancer is higher in African Caribbean men than in French Caucasian men. Specificities of the former could be explained by genomic events linked with key genes such as DNA damage pathway genes PARP1, CDK12, and the oncogenic long non-coding RNA gene PVT1 at the 8q24 prostate cancer susceptibility locus.

KEYWORDS:

African ancestry; Caribbean; Mutation; Prostate cancer

PMID:
30245085
DOI:
10.1016/j.eururo.2018.08.026
[Indexed for MEDLINE]

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