Germline sequencing in men with metastatic castration-resistant prostate cancer from the BARCODE2 study reveals a wide range of pathogenic variants in DNA repair genes
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Date
2024-02-15Author
Benafif, S
Jones, A-B
Merson, S
Rageevakumar, R
McGrowder, E
Tyler, M
Cafferty, F
Hogben, M
Hussain, N
Bancroft, E
Reid, A
Wakerell, S
Karlsson, Q
Saunders, E
Whitmore, I
Sorensen, KD
Dennis, N
Black, E
Wood, A
Richards, K
Lees, K
Perna, C
Falconer, A
Mills, J
Hughes, R
Kumar, S
Mikropoulos, C
Burnett, S
Attard, G
Hall, E
Kote-Jarai, Z
Eeles, R
Type
Journal Article
Metadata
Show full item recordAbstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>The presence of germline mutations plays an increasingly important role in risk assessment and treatment of prostate cancer (PrCa). Screening for high-risk mutations in subsets of patients is becoming routine. We explore the prevalence of germline genetic mutations in men with metastatic castration-resistant prostate cancer (mCRPC) recruited to the BARCODE2 trial.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>The BARCODE2 trial is a two-part study investigating the response to carboplatin chemotherapy in mCRPC patients carrying a germline variant in a DNA repair gene (DRG). We report interim data from Part 1, in which participants are recruited for germline genetic testing using a customised next-generation sequencing panel consisting of 115 genes.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>These interim results (<jats:italic>N</jats:italic> = 220) demonstrate a similar frequency of germline DRG variants in mCRPC patients compared with previously published data (15% detection rate). No significant clinical differences were identified between all carriers and non-carriers, though <jats:italic>BRCA2/ATM</jats:italic> carriers were found to have a shorter time to mCRPC diagnosis.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Germline pathogenic/likely pathogenic (P/LP) variants in <jats:italic>BRCA2 and ATM</jats:italic> genes are associated with a shorter time to progression and rarer P/LP variants in other DRG genes may play a role in mCRPC. This justifies the use of routine screening of men with advanced PrCa for germline variants and supports the need for an expanded panel test.</jats:p>
</jats:sec>
Collections
Research team
Clin Trials & Stats Unit
Language
eng
Date accepted
2023-11-19
License start date
2024-02-15
Citation
BJC Reports, 2024, 2 (1),
Publisher
Springer Science and Business Media LLC