| Summary: | Objective To investigate the mutations in the tissue DNA and plasma circulating tumor DNA (ctDNA) from patients with prostate cancer, and analyze their association with clinical characteristics and treatment. Methods Based on probe hybridization capture and Illumina high-throughput sequencing, a targeted second-generation sequencing was used to analyze the mutations in 31 tumor tissues and 32 peripheral blood specimens from 46 patients with pathologically diagnosed prostate cancer. The tumor tissues and peripheral blood specimens were sequenced in the whole exons area and part of the introns area of 1 021 genes for 4 types of mutations (point mutation, loss/insert of small fragments, copy number variation and currently known fusion genes). Results The most frequently mutated gene was TP53 (29.0%, 9/31), followed by CDK12 (22.6%, 7/31), FOXA1 (22.6%, 7/31) and JAK1 (16.1%, 5/31) in 31 tissue samples. The most common mutant genes in the 32 blood samples were AR (34.3%, 11/32), APC (25.0%, 8/32), CDK12 (18.8%, 6/32), DNMT3a (18.8%, 6/32) and TP53 (18.8%, 6/32). TMPRSS2-ERG fusion gene was detected in 13.0% (6/46) of the 46 patients. One patient had TMPRSS2-ERG, VEGFA-TMPRSS2, and ERG-VEGFA fusion mutations simultaneously. The somatic mutation of homologous recombination (HR) associated genes were found in 21.7% (10/46) of all the patients, and those with germline mutations in the HR gene accounted for 8.7% (4/46) of all the patients. Moreover, the patients with HR gene mutations (either germline or somatic), especially those with germline mutations, had younger onset-age, higher Gleason score, and more metastases. Conclusion Gene mutation can be detected from both blood ctDNA and traditional tissue DNA. Dynamic blood ctDNA testing can monitor the changes in gene spectrum of prostate cancer, and is helpful to adjust treatment scheme in time.
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