Clinical determinants for successful circulating tumor DNA analysis in prostate cancer.

Clinical determinants for successful circulating tumor DNA analysis in prostate cancer.

Publication date: Mar 13, 2019

Plasma-based cell-free DNA is an attractive biospecimen for assessing somatic mutations due to minimally-invasive real-time sampling. However, next generation sequencing (NGS) of cell-free DNA (cfDNA) may not be appropriate for all patients with advanced prostate cancer (PC).

Blood was obtained from advanced PC patients for plasma-based sequencing. UW-OncoPlex, a ∼2 Mb multi-gene NGS panel performed in the CLIA/CAP environment, was optimized for detecting cfDNA mutations. Tumor tissue and germline samples were sequenced for comparative analyses. Multivariate logistic regression was performed to determine the clinical characteristic associated with the successful detection of somatic cfDNA alterations (ie detection of at least one clearly somatic PC mutation).

Plasma for cfDNA sequencing was obtained from 93 PC patients along with tumor tissue (N = 67) and germline (N = 93) controls. We included data from 76 patients (72 prostate adenocarcinoma; 4 variant histology PC) in the analysis. Somatic DNA aberrations were detected in 34 cfDNA samples from patients with prostate adenocarcinoma. High PSA level, high tumor volume, and castration-resistance were significantly associated with successful detection of somatic cfDNA alterations. Among samples with somatic mutations detected, the cfDNA assay detected 93/102 (91%) alterations found in tumor tissue, yielding a clustering-corrected sensitivity of 92% (95% confidence interval 88-97%). All germline pathogenic variants present in lymphocyte DNA were also detected in cfDNA (N = 12). Somatic mutations from cfDNA were detected in 30/33 (93%) instances when PSA was >10 ng/mL.

Disease burden, including a PSA >10 ng/mL, is strongly associated with detecting somatic mutations from cfDNA specimens.

Schweizer, M.T., Gulati, R., Beightol, M., Konnick, E.Q., Cheng, H.H., Klemfuss, N., De Sarkar, N., Yu, E.Y., Montgomery, R.B., Nelson, P.S., and Pritchard, C.C. Clinical determinants for successful circulating tumor DNA analysis in prostate cancer. 04207. 2019 Prostate.

Concepts Keywords
Aberrations Carcinoma
Assay Germline
Castration Somatic
Clustering Prostate cancer
Confidence Interval Genetics
Disease Burden Anatomical pathology
Gene Circulating free DNA
Germline Developmental biology
Histology RTT
Logistic Regression DNA
Lymphocyte Branches of biology
Minimally Invasive CfDNA mutations Tumor
Pathogenic Prostate adenocarcinoma
PC
Plasma
Prostate
Prostate Adenocarcinoma
Prostate Cancer
Sequencing
Somatic
Somatic Mutation
Somatic Mutations
Tumor

Semantics

Type Source Name
gene UNIPROT PROS1
gene UNIPROT PLAG1
gene UNIPROT NPEPPS
gene UNIPROT PSAT1
gene UNIPROT KLK3
disease DOID prostate adenocarcinoma
gene UNIPROT SERPINB6
gene UNIPROT SORBS1
gene UNIPROT BRD4
gene UNIPROT HACD1
gene UNIPROT LNPEP
gene UNIPROT CAP1
disease MESH multi
pathway BSID Prostate cancer
disease DOID prostate cancer
disease MESH prostate cancer
disease MESH tumor

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