Investig Clin Urol.  2019 Jul;60(4):227-234. 10.4111/icu.2019.60.4.227.

Genomic analysis of Korean patients with advanced prostate cancer by use of a comprehensive next-generation sequencing panel and low-coverage, whole-genome sequencing

• Kang M
• Cho E
• Jang J
• Lee J
• Jeon Y
• Jeong BC
• Seo SI
• Jeon SS
• Lee HM
• Choi HY
• Jeon HG

• KMID: 2450539
• DOI: http://doi.org/10.4111/icu.2019.60.4.227

Abstract

PURPOSE
To analyze the characteristics of somatic mutations and copy number alterations (CNAs) in Korean patients with advanced prostate cancer (PCa) by use of the Oncomine Comprehensive Panel (ThermoFisher Scientific) and low-coverage, whole-genome sequencing (LC-WGS).
MATERIALS AND METHODS
We retrospectively analyzed PCa tissues obtained from 14 patients with advanced PCa (metastatic tumor, 12 [85.7%]; nonmetastatic castration-resistant PCa, 1 [7.1%]; pT3b, 1 [7.1%]) from 2009 to 2017. The Oncomine Comprehensive Panel included a total of 143 genes. Moreover, LC-WGS was performed to detect CNAs of the entire genome. Two plasma samples matched with tumor tissues were analyzed using LC-WGS to compare the chromosomal aberration patterns between circulating tumor DNA and tumor tissue.
RESULTS
Genetic alterations were most frequently observed in the androgen receptor (AR) (42.9%, n=6/14), TP53 (14.3%, n=2/14), and PTEN (14.3%, n=2/14) genes in the Oncomine panel. AR amplification was the most common CNA (35.7%, n=5/14). As a result of LC-WGS, CNAs were confirmed in about 92.9% (n=13/14) of the samples in regions Xq12, 8q24.21, and 11q13.3 (gains) and in regions 6q16.1, 8p23.1, 10q25.1, 16q24.2, 18q12.3, Xq25, and Xq26.3 (losses). All CNAs identified in the Oncomine panel matched the results of LC-WGS. Additionally, LC-WGS of two plasma samples that matched tumor tissues revealed that CNA patterns of plasma samples (circulating tumor DNA) were very similar to those detected in tumor samples.
CONCLUSIONS
Our data showed that the characteristics of mutations and CNAs in Korean patients with advanced PCa were similar to those observed in previous studies.

Keyword

Prostatic neoplasms; Sequence analysis, DNA; Whole genome sequencing

MeSH Terms

Chromosome Aberrations
DNA
Genome
Humans
Passive Cutaneous Anaphylaxis
Plasma
Prostate*
Prostatic Neoplasms*
Receptors, Androgen
Retrospective Studies
Sequence Analysis, DNA
DNA
Receptors, Androgen

Figure

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  Fig. 1 Genomic alterations detected in 14 patients with advanced prostate cancer by use of the Oncomine Comprehensive Panel.

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  Fig. 2 Circos plot of low-coverage, whole-genome sequencing analysis of 14 patients with advanced prostate cancer. The innermost sample has the lowest copy number alterations, and the outermost has the highest copy number alterations.

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  Fig. 3 Comparison of copy number alterations by low-coverage, whole-genome sequencing between circulating tumor DNA (ctDNA) and cancer tissues from two patients (A and B) with metastatic prostate cancer.

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