scholarly journals Tumor Cell–Free DNA Copy Number Instability Predicts Therapeutic Response to Immunotherapy

2017 ◽  
Vol 23 (17) ◽  
pp. 5074-5081 ◽  
Author(s):  
Glen J. Weiss ◽  
Julia Beck ◽  
Donald P. Braun ◽  
Kristen Bornemann-Kolatzki ◽  
Heather Barilla ◽  
...  
Author(s):  
Glen J. Weiss ◽  
Julia Beck ◽  
Donald P. Braun ◽  
Kirsten Bornemann-Kolatzki ◽  
Heather Barilla ◽  
...  

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 3027-3027 ◽  
Author(s):  
Glen J. Weiss ◽  
Julia Beck ◽  
Donald Peter Braun ◽  
Kirsten Bornemann-Kolatzki ◽  
Heather Barilla ◽  
...  

Author(s):  
Kayo Kashiwada‐Nakamura ◽  
Tselmeg Mijiddorj Myangat ◽  
Ikko Kajihara ◽  
Hisashi Kanemaru ◽  
Soichiro Sawamura ◽  
...  

2018 ◽  
Vol 64 (9) ◽  
pp. 1338-1346 ◽  
Author(s):  
Shobha Silva ◽  
Sarah Danson ◽  
Dawn Teare ◽  
Fiona Taylor ◽  
James Bradford ◽  
...  

Abstract BACKGROUND A substantial number of melanoma patients develop local or metastatic recurrence, and early detection of these is vital to maximise benefit from new therapies such as inhibitors of BRAF and MEK, or immune checkpoints. This study explored the use of novel DNA copy-number profiles in circulating cell-free DNA (cfDNA) as a potential biomarker of active disease and survival. PATIENTS AND METHODS Melanoma patients were recruited from oncology and dermatology clinics in Sheffield, UK, and cfDNA was isolated from stored blood plasma. Using low-coverage whole-genome sequencing, we created copy-number profiles from cfDNA from 83 melanoma patients, 44 of whom had active disease. We used scoring algorithms to summarize copy-number aberrations and investigated their utility in multivariable logistic and Cox regression analyses. RESULTS The copy-number aberration score (CNAS) was a good discriminator of active disease (odds ratio, 3.1; 95% CI, 1.5–6.2; P = 0.002), and CNAS above or below the 75th percentile remained a significant discriminator in multivariable analysis for active disease (P = 0.019, with area under ROC curve of 0.90). Additionally, mortality was higher in those with CNASs above the 75th percentile than in those with lower scores (HR, 3.4; 95% CI, 1.5–7.9; P = 0.005), adjusting for stage of disease, disease status (active or resected), BRAF status, and cfDNA concentration. CONCLUSIONS This study demonstrates the potential of a de novo approach utilizing copy-number profiling of cfDNA as a biomarker of active disease and survival in melanoma. Longitudinal analysis of copy-number profiles as an early marker of relapsed disease is warranted.


2017 ◽  
Vol 11 (8) ◽  
pp. 1099-1111 ◽  
Author(s):  
Jian Li ◽  
Rachel L. Dittmar ◽  
Shu Xia ◽  
Huijuan Zhang ◽  
Meijun Du ◽  
...  

2016 ◽  
Vol 42 (11) ◽  
pp. S245
Author(s):  
Shobha Silva ◽  
Dawn Teare ◽  
James Bradford ◽  
Ian Brock ◽  
Daniel Connley ◽  
...  

2021 ◽  
pp. 172460082199235
Author(s):  
Weina Zhang ◽  
Yu-min Zhang ◽  
Yuan Gao ◽  
Shengmiao Zhang ◽  
Weixin Chu ◽  
...  

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors. Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled. Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy ( P<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975. Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.


2016 ◽  
Vol 36 (6) ◽  
pp. 584-586 ◽  
Author(s):  
Cheryl A. Mather ◽  
Zhongxia Qi ◽  
Arun P. Wiita

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