Abstract:
BACKGROUND:There is a lack of molecularly-informed biomarkers for patients with metastatic renal cell carcinoma (RCC). Plasma cell-free DNA (cfDNA) sequencing is a minimally-invasive alternative to tissue for profiling the genome in other cancers but relevance in metastatic RCC remains unclear. MATERIALS AND METHODS:Whole blood was collected from 55 patients with metastatic RCC. Plasma cfDNA and leukocyte DNA were subjected to targeted sequencing across 981 cancer genes. Matched tumor tissue from 14 patients was analyzed. RESULTS:Thirty-three percent of patients had evidence for RCC-derived circulating tumor DNA (ctDNA), significantly lower than patients with metastatic prostate or bladder cancer analyzed using the same approach. Among ctDNA-positive patients, ctDNA fraction averaged only 3.9% and showed no strong association with clinical variables. In these patients, the most commonly mutated genes were VHL, BAP1, and PBRM1, and matched tissue concordance was 77%. Evidence of somatic expansions unrelated to RCC, such as clonal hematopoiesis of indeterminate potential, were detected in 43% of patients. Pathogenic germline mutations in DNA repair genes were detected in 11% of patients. CtDNA-positive patients had shorter overall survival and progression-free survival on first-line therapy. Patients with evidence of clonal hematopoiesis of indeterminate potential had an intermediate prognosis compared with ctDNA-positive and -negative patients. CONCLUSIONS:CfDNA sequencing enables straightforward characterization of the somatic RCC genome in a minority of patients with metastatic RCC. Owing to low ctDNA abundance, and the presence of non-RCC derived somatic clones in circulation, cfDNA sequencing may not be a simple pan-patient alternative to tissue biopsy in metastatic RCC.
journal_name
Clin Genitourin Cancerjournal_title
Clinical genitourinary cancerauthors
Bacon JVW,Annala M,Soleimani M,Lavoie JM,So A,Gleave ME,Fazli L,Wang G,Chi KN,Kollmannsberger CK,Wyatt AW,Nappi Ldoi
10.1016/j.clgc.2019.12.018subject
Has Abstractpub_date
2020-08-01 00:00:00pages
322-331.e2issue
4eissn
1558-7673issn
1938-0682pii
S1558-7673(19)30391-Xjournal_volume
18pub_type
杂志文章abstract:BACKGROUND:Androgen receptor (AR) signaling remains important in castration-resistant prostate cancer (CRPC) and sequential responses to hormonal therapies are observed. Little is known about the factors associated with responsiveness to secondary hormone therapy (HT). METHODS:We retrospectively identified patients wi...
journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
doi:10.1016/j.clgc.2011.06.006
更新日期:2011-12-01 00:00:00
abstract::Testicular germ cell tumors (TGCTs) represent the most common solid tumors among men aged 15 to 34 years. Fortunately, recent advances have made testicular cancer a highly curable disease. Despite the high cure rates, there are still several areas in testis cancer care where treatment decisions are controversial and g...
journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,评审
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,meta分析
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
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更新日期:2019-06-01 00:00:00
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
doi:10.1016/j.clgc.2016.03.009
更新日期:2016-10-01 00:00:00
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
doi:10.3816/CGC.2006.n.006
更新日期:2006-03-01 00:00:00
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journal_title:Clinical genitourinary cancer
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更新日期:2020-04-01 00:00:00
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
doi:10.1016/j.clgc.2015.08.004
更新日期:2016-06-01 00:00:00
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journal_title:Clinical genitourinary cancer
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更新日期:2016-06-01 00:00:00
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,多中心研究
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journal_title:Clinical genitourinary cancer
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更新日期:2016-08-01 00:00:00
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,多中心研究
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更新日期:2020-02-01 00:00:00
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,meta分析
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,评审
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journal_title:Clinical genitourinary cancer
pub_type: 杂志文章,多中心研究
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