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

被引：29

作者：

Tonon, Laurie ^{[1
]}

Fromont, Gaelle ^{[2
,4
,11
]}

Boyault, Sandrine ^{[10
]}

Thomas, Emilie ^{[1
]}

Ferrari, Anthony ^{[1
]}

Sertier, Anne-Sophie ^{[1
]}

Kielbassa, Janice ^{[1
]}

Le Texier, Vincent ^{[1
]}

Kamoun, Aurelie ^{[12
]}

Elarouci, Nabila ^{[12
]}

Irani, Jacques ^{[4
]}

Multigner, Luc ^{[5
]}

Gut, Ivo Glynne ^{[6
,7
]}

Gut, Marta ^{[6
,7
]}

Blanchet, Pascal ^{[5
,8
]}

De Reynies, Aurelien ^{[12
]}

Cancel-Tassin, Geraldine ^{[2
,3
]}

Viari, Alain ^{[1
,13
]}

Cussenot, Olivier ^{[2
,3
,9
]}

机构：

[1] Ctr Leon Berard, Plateforme Bioinformat Gilles Thomas, Synergie Lyon Canc, Lyon, France

[2] CeRePP, Paris, France

[3] Sorbonne Univ, GRC 5, ONCOTYPE URO, Paris, France

[4] CHU Poitiers, Hop Miletrie, Poitiers, France

[5] Inserm U1085, IRSET, Pointe a Pitre, Guadeloupe, France

[6] Barcelona Inst Sci & Technol, CNAG CRG, Ctr Genom Regulat, Barcelona, Spain

[7] Univ Pompeu Fabra, Barcelona, Spain

[8] CHU Pointe A Pitre Abymes, Dept Urol, Pointe a Pitre, Guadeloupe, France

[9] Acad Hosp Paris Est, AP HP, Dept Urol, Paris, France

[10] Ctr Leon Berard, Dept Rech Translat & Innovat, Genom Canc, Lyon, France

[11] CHRU Tours, Dept Pathol, Tours, France

[12] Ligue Natl Le Canc, Programme Cartes Identite Tumeurs CIT, Paris, France

[13] INRIA, Montbonnot St Martin, France

来源：

EUROPEAN UROLOGY | 2019年 / 75卷 / 01期

关键词：

African ancestry; Caribbean; Mutation; Prostate cancer; GUADELOUPE;

D O I：

10.1016/j.eururo.2018.08.026

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 (C) 2018 Published by Elsevier B.V. on behalf of European Association of Urology.

引用

页码：11 / 15

页数：5

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