Investig Clin Urol.  2020 Mar;61(2):127-135. 10.4111/icu.2020.61.2.127.

Targeted next-generation sequencing for locally advanced prostate cancer in the Korean population

• Suh J
• Jeong CW
• Choi S
• Ku JH
• Kim HH
• Kim KS
• Kwak C

• KMID: 2471068
• DOI: http://doi.org/10.4111/icu.2020.61.2.127

Abstract

PURPOSE
This study aimed to evaluate the feasibility of pan-cancer panel analysis for locally advanced prostate cancer in the Korean population.
MATERIALS AND METHODS
We analyzed 20 patients with locally advanced prostate cancer who underwent radical prostatectomy. A pan-cancer panel (1.9 Mbp) developed by Seoul National University Hospital (SNUH), composed of 183 target genes, 23 fusion genes, and 45 drug target regions was used for this analysis. We compared the SNUH pan-cancer panel results with The Cancer Genome Atlas (TCGA) database to search for different mutations in the Korean population. Clinical data were analyzed with univariate and multivariate analysis, and p-values <0.05 were considered statistically significant. Kaplan-Meier curve and log-rank tests were performed to evaluate survival.
RESULTS
The average age of the patients and initial prostate-specific antigen values were 69.3±7.8 years and 66.3±16.9 ng/dL, respectively. Average sequencing depth was 574.5±304.1×. Ninety-nine genetic mutations and 5 fusions were detected. SPOP (25%), KMT2D (20%), and BRAF (15%) were frequently detected. ERG fusions were recurrently detected in 20% of the patients, with SLMAP and SETD4 as novel fusion partners. BRAF mutation was frequently detected in this study, but not in the TCGA database. Multivariate analysis showed BRAF mutation as an independent prognostic factor for biochemical recurrence (hazard ratio, 9.84; p=0.03).
CONCLUSIONS
The pan-cancer panel comprising genes related to prostate cancer is a useful tool for evaluating genetic alterations in locally advanced prostate cancers. Our results suggest that the BRAF mutation is associated with biochemical recurrence in the Korean population.

Keyword

Genetics; Prostate-specific antigen; Prostatic neoplasms; Recurrence

MeSH Terms

Genetics
Genome
Humans
Multivariate Analysis
Prostate*
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms*
Recurrence
Seoul
Prostate-Specific Antigen

Figure

• 

  Fig. 1 Specific genetic alteration counts of each patient. A minimum of 1 to a maximum of 13 mutations per patient were found by multi-cancer panel analysis. Blue bars show SNP and Indel mutations and orange bars show number of structural variations.

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  Fig. 2 Integrative analysis of cancer panel analysis of 20 patients. Each grey column represents specific data for 1 of the 20 patients in order. Genomic polymorphism of SNP/Indel mutation by truncating, in the frame, missense is noted by a color dot in a grey column with black, brown, and green. Structural variation was found in 5 patients annotated by purple color; the most common finding was ERG: TMPRSS2 fusion. No CNV amplification was found by our targeted next-generation sequencing (NGS) panel. This oncoprint was obtained by use of The cBioPortal for Cancer Genomics (http://cbioportal.org) graphic visualization Genetic alteration tool.

• 

  Fig. 3 Kaplan–Meier curve of BRAF mutation on biochemical recurrence with the log-rank test. Positive BRAF mutation worsened biochemical-recurrence-free survival with statistically significant difference (p=0.03).

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