In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 457-457
Abstract:
457 Background: Biomarkers are urgently needed to facilitate tumor molecular stratification in metastatic urothelial carcinoma (mUC), thus potentially enabling patient selection for targeted- and immuno-therapies. We aimed to assess concordance for clinically-relevant driver gene alterations between same-patient tumor tissue and ctDNA. Methods: Whole blood samples were collected from 90 mUC patients (162 samples in total) for next-generation sequencing of cell-free DNA (cfDNA) and leukocyte DNA. Deep targeted sequencing was performed across a custom 50 bladder cancer gene panel (median cfDNA depth of 986x). Matched archival primary tissue and/or metastatic tissue biopsy was available from 65 patients, and profiled using the same assay. Results: 81% of mUC patients (73/90) had ctDNA fractions above 2% in at least one blood collection (median ctDNA fraction 22%). A high tumor mutation burden (≥25 mutations per Mb) was observed in ctDNA from 20 patients (27%). From ctDNA, TP53 and ARID1A were mutated in 64% and 29% of patients, respectively. Tissue from distant metastatic lesions was available from 17 patients; 82% (62/76) of coding somatic mutations identified were independently detected in the matched ctDNA sample; however, 7/14 discordant calls were attributable to the paired sample having a low ctDNA fraction. Similarly, 89% (88/99) of coding somatic mutations detected in archival primary tissue (cystectomy or nephrectomy) were present in later cfDNA collections. Sequencing multiple sites from archival cystectomies revealed spatially and genomically distinct subclones in 2/4 cases. Conclusions: In mUC, tumor tissue and ctDNA demonstrate remarkably high concordance; our findings support the use of either approach in the characterization of truncal driver gene alterations.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.7_suppl.457
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
