Prostate cancer(Pca) is one of the most common types of cancer in men. Androgen deprivation therapy(ADT) is the main choice of Pca treatment. However, major investigations have focussed on caucasians population. Here, we intended to explore the molecular characteristics and clinical characteristics between localized and metastatic of Chinese Pca patients.
29 Pca patients with localized or metastatic tumor were enrolled. Somatic and germline mutations were identified via targeted next generation sequencing with Acornmed panel including 808 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA) and chromosomal rearrangements. Clinical data of the cohort was collected and analyzed.
Median age was 68 yrs (range 53-80), 62% were classified as metastatic(M), and 17% had received one prior ADT drug. The most common somatic mutations were observed in TP53(24%), FOXA1(21%), CDK12(17%), AR(10%), KRAS(7%), PIK3CA(7%), SPOP(7%), PTCH1(7%), ATM(7%) and TSC2(3%) genes. Median tumor mutational burden (TMB) was 7 Mus/ Mb(1-22). Germline pathogenic or likely pathogenic mutations occurred 17% of Pca patients, 4/5 mutations were DNA damage response genes, and 4 patients had metastatic Pca. AR was shared by both localized and metastatic Pca (2 in ADT- and 1 in ADT+). Mutated CDK12 was only detected in patients without any history of ADT drug(3 in M- and 2 in M+). Interestingly, Tp53 mutations were only detected in metastatic Pca(7/18 M+). FOXA1 mutations were observed more frequently in patients with localized Pca(4/11M- versus 2/18 M+).
These findings show differences in the genomics alterations of metastatic and localized prostate cancer. Germline mutations are more likely to be detected in patients with advanced prostate cancer. Mutations in the TP53 gene are more common in advanced prostate cancer. Additional correlative analyses are ongoing.
The authors.
Has not received any funding.
T. Yang, H. Wang, F. Lou, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd., All other authors have declared no conflicts of interest.