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

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.

• Authors: Minyong Kang, Eunhae Cho, Jahyun Jang, Junnam Lee, Youngjoo Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Hwang Gyun Jeon
• Journal: Investigative and clinical urology (Investig Clin Urol) Vol. 60 Issue 4 Pg. 227-234 (07 2019) ISSN: 2466-054X [Electronic] Korea (South)
• PMID: 31294131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm

Topics

• Aged
• Aged, 80 and over
• DNA Copy Number Variations
• DNA, Neoplasm (analysis)
• Genomics
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Prostatic Neoplasms (genetics, pathology)
• Republic of Korea
• Retrospective Studies
• Whole Genome Sequencing