Abstract 5397: Characterizing the genomic landscape of bladder cancer with circulating tumor DNA

Tumor in situ fluid (TISF) refers to the fluid at the local surgical cavity. We evaluated the feasibility of TISF-derived circulating tumor DNA (ctDNA) characterizing the genomic landscape for glioma. This retrospective study included TISF and tumor samples from 10 patients with glioma, we extracted cell-free DNA (cfDNA) from the TISF and then performed deep sequencing on that. And we compared genomic alterations between TISF and tumor tissue. Results showed that the concentration of cfDNA fragments from the patients for TISF ranged from 7.2 to 1,397 ng/ml. At least one tumor-specific mutation was identified in all 10 patients (100%). Further analysis of TISF ctDNA revealed a broad spectrum of genetic mutations, which have been reported to have clinical relevance. The analysis of concordance between TISF and tumor tissue reflected the spatiotemporal heterogeneity of glioma. Collectively, TISF ctDNA was a powerfully potential source for characterizing the genomic landscape of glioma, which provided new possibilities for precision medicine in patients with glioma.

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Somatic genomic landscape of over 15,000 patients with advanced-stage cancer from clinical next-generation sequencing analysis of circulating tumor DNA.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.lba11501 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. LBA11501-LBA11501 ◽

Cited By ~ 8

Author(s):

Oliver A. Zill ◽

Stefanie Mortimer ◽

Kimberly C. Banks ◽

Rebecca J Nagy ◽

Darya Chudova ◽

...

Keyword(s):

Next Generation Sequencing ◽

Circulating Tumor Dna ◽

Sequencing Analysis ◽

Advanced Stage ◽

Next Generation ◽

Genomic Landscape ◽

Next Generation Sequencing Analysis ◽

Advanced Stage Cancer ◽

Tumor Dna ◽

Generation Sequencing

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Circulating tumor DNA-targeted sequencing to reveal germline and somatic alterations that can guide decision-making in metastatic castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17556 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17556-e17556

Author(s):

Baijun Dong ◽

Liancheng Fan ◽

Bin Yang ◽

Wei Chen ◽

Yonghong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Circulating Tumor Dna ◽

Targeted Sequencing ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Genomic Landscape ◽

Platinum Based Chemotherapy ◽

Somatic Alterations ◽

Multiple Treatments ◽

Tumor Dna

e17556 Background: The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is dynamic with the application of multiple treatments. The circulating tumor DNA (ctDNA), which reveals germline and somatic alterations, provides a mini-invasive tool for monitoring tumor evolution. Methods: We performed an exploratory analysis of 299 ctDNA samples from 8 centers through application of multiple-gene deep targeted sequencing. Results: The most common recurrent genomic alterations were in AR(34.7%), TP53(18.9%), CDK12(15.4%), BRCA2(13.3%), and the majority of these clinically actionable gene alterations were identified in somatic level (CDK12 100% in somatic). The results showed the frequency of AR amplification and TP53 defect significantly increased in post-second and later line treatment group compared with treatment-naive group. AR amplification and TP53 or RB1 defect were associated with resistance to abiraterone or docetaxel. CDK12 was more frequently altered in our cohort than those in previous reports which mainly focused on Caucasian population. The patients with CDK12 defect showed rapid resistance to abiraterone and limited efficacy of Poly (ADP-ribose) polymerase inhibitors (PARPi). However, these patients seemed to benefit from chemotherapy, especially platinum-based chemotherapy. Conclusions: This multi-institutional real-world study explored the genomic landscape and captured the significant diversity of mCRPC at different treatment stages by liquid biopsy. These findings established genomic drivers associated with resistance to multiple treatments (including PARPi and platinum-based chemotherapy) in mCRPC. Hence, ctDNA targeted sequencing can help guide clinical decision making in mCRPC throughout the whole treatment process. CDK12 might be able to be a novel predictive biomarker to guide treatment selection in mCRPC.

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Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.657483 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jinghua Zhang ◽

Daofeng Dai ◽

Junqiang Tian ◽

Lifeng Li ◽

Jing Bai ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Size ◽

Disease Free Survival ◽

Disease Recurrence ◽

Circulating Tumor Dna ◽

Targeted Sequencing ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive ◽

Tumor Dna

Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.

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Evolution of the genomic landscape of circulating tumor DNA (ctDNA) in advanced prostate cancer (aPC) over treatment and time.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.5052 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 5052-5052 ◽

Cited By ~ 1

Author(s):

David D. Stenehjem ◽

Andrew W Hahn ◽

Roberto Nussenzveig ◽

Emma Carroll ◽

David Michael Gill ◽

...

Keyword(s):

Prostate Cancer ◽

Advanced Prostate Cancer ◽

Circulating Tumor Dna ◽

Genomic Landscape ◽

Tumor Dna

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Circulating tumor DNA-targeted sequencing to reveal germline and somatic alterations that can guide decision-making in metastatic castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.173 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 173-173

Author(s):

Baijun Dong ◽

Liancheng Fan ◽

Bin Yang ◽

Wei Chen ◽

Yonghong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Decision Making ◽

Circulating Tumor Dna ◽

Targeted Sequencing ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Genomic Landscape ◽

Somatic Alterations ◽

Multiple Treatments ◽

Tumor Dna

173 Background: The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is dynamic with the application of multiple treatments. The circulating tumor DNA(ctDNA), which reveals germline and somatic alterations, provides a mini-invasive tool for monitoring tumor evolution. Methods: We performed an exploratory analysis of 299 ctDNA samples from 8 centers through application of multiple-gene deep targeted sequencing. Results: The most common recurrent genomic alterations were in AR(34.7%), TP53(18.9%), CDK12(15.4%), BRCA2(13.3%), and the majority of these clinically actionable gene alterations were identified in somatic level(CDK12 100% in somatic). The results showed the frequency of AR amplification and TP53 defect significantly increased in post-second and later line treatment group compared with treatment-naive group. AR amplification and TP53 or RB1 defect were associated with resistance to abiraterone or docetaxel. CDK12 was more frequently altered in our cohort than those in previous reports which mainly focused on Caucasian population. The patients with CDK12 defect showed rapid resistance to abiraterone and limited efficacy of PARPi. However, these patients seemed to benefit from chemotherapy, espeacially platnium-based chemotherapy. Conclusions: This multi-institutional real-world study explored the genomic landscape and captured the significant diversity of mCRPC at different treatment stages by liquid biopsy. These findings established genomic drivers associated with resistance to multiple treatments (including PARPi and platinum-based chemotherapy) in mCRPC. Hence, ctDNA targeted sequencing can help guide clinical decision making in mCRPC throughout the whole treatment process. CDK12 might be able to be a novel predictive biomarker to guide treatment selection in mCRPC.

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