scholarly journals Author response: Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death

2018 ◽  
Author(s):  
Haley Hieronymus ◽  
Rajmohan Murali ◽  
Amy Tin ◽  
Kamlesh Yadav ◽  
Wassim Abida ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Author Response ◽  
Pan Cancer

scholarly journals Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Haley Hieronymus ◽  
Rajmohan Murali ◽  
Amy Tin ◽  
Kamlesh Yadav ◽  
Wassim Abida ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Cancer Survival ◽  
Cancer Type ◽  
Primary Prostate Cancer ◽  
Tumor Genome ◽  
Pan Cancer ◽  
Prognostic Association

The level of copy number alteration (CNA), termed CNA burden, in the tumor genome is associated with recurrence of primary prostate cancer. Whether CNA burden is associated with prostate cancer survival or outcomes in other cancers is unknown. We analyzed the CNA landscape of conservatively treated prostate cancer in a biopsy and transurethral resection cohort, reflecting an increasingly common treatment approach. We find that CNA burden is prognostic for cancer-specific death, independent of standard clinical prognosticators. More broadly, we find CNA burden is significantly associated with disease-free and overall survival in primary breast, endometrial, renal clear cell, thyroid, and colorectal cancer in TCGA cohorts. To assess clinical applicability, we validated these findings in an independent pan-cancer cohort of patients whose tumors were sequenced using a clinically-certified next generation sequencing assay (MSK-IMPACT), where prognostic value varied based on cancer type. This prognostic association was affected by incorporating tumor purity in some cohorts. Overall, CNA burden of primary and metastatic tumors is a prognostic factor, potentially modulated by sample purity and measurable by current clinical sequencing.

Tumor copy number alteration (CNA) burden as a prognostic factor for overall survival in Chinese gastric cancers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15555-e15555
Author(s):  
Bo Han ◽  
Dandan Ren ◽  
Beibei Mao ◽  
Xue Song ◽  
Wanning Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Surgical Resection ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Clinical Staging ◽  
Survival Prediction ◽  
High Morbidity ◽  
Gastric Cancers

e15555 Background: Gastric cancer (GC) is associated with high morbidity and mortality rates in the world with poor prognosis and limited treatment options. The level of copy number alteration (CNA), termed CNA burden, is reported as a pan-cancer prognostic factor associated with recurrence and death. The current study aims to investigate association between CNA burden in primary tumor tissue and overall survival (OS) of Chinese patients with GC after surgical resection. Methods: The present study included 78 patients who had received surgical resection and adjuvant chemotherapy with poorly differentiated GC. The primary outcome was OS. Tumor specimens were obtained from surgery and submitted for next generation sequencing (NGS) with matched normal tissue samples. A 1408-gene panel was used to identify genome profiles. Data were analyzed using Cox proportional hazards models and Kaplan-Meier survival analysis. Results: The most frequently altered genes were TP53 (47%), PIK3CA (10%), PTEN (9%), NOTCH1 (8%) and RNF43 (6%), and copy numbers of TRPS1 (65%), COL1A2 (50%), CSMD3 (45%), ZFHX4 (45%), NAV3 (36%) varied most frequency in current cohort. Greater tumor CNA burden correlated with an increase in death from disease compared to a lower tumor CNA burden ( p= 0.0066). In addition, there were statistically significant differences in OS between different clinical staging ( p= 0.0011). Moreover, the Cox proportional hazard model showed that CNA burden was an independent prognosis factor in GC. Finally, we performed an independent signature that includes CNA burden and clinical staging to predict survival of GC. Conclusions: This study indicates that tumor CNA burden is an independent predictive survival biomarker for Chinese gastric cancers. CNA burden combined with clinical staging is a better predictor for postoperative survival prediction of gastric cancer.

scholarly journals Pan-cancer patterns of somatic copy number alteration

2013 ◽  
Vol 45 (10) ◽  
pp. 1134-1140 ◽  
Author(s):  
Travis I Zack ◽  
Steven E Schumacher ◽  
Scott L Carter ◽  
Andrew D Cherniack ◽  
Gordon Saksena ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Alteration ◽  
Pan Cancer ◽  
Somatic Copy Number Alteration

scholarly journals Patient-Specific Network for Personalized Breast Cancer Therapy with Multi-Omics Data

Entropy ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 225
Author(s):  
Claudia Cava ◽  
Soudabeh Sabetian ◽  
Isabella Castiglioni
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Protein Interaction Network ◽  
Copy Number ◽  
Tumor Heterogeneity ◽  
Copy Number Alteration ◽  
Interaction Network ◽  
Computational Approach ◽  
Patient Specific ◽  
Basal Breast Cancer

The development of new computational approaches that are able to design the correct personalized drugs is the crucial therapeutic issue in cancer research. However, tumor heterogeneity is the main obstacle to developing patient-specific single drugs or combinations of drugs that already exist in clinics. In this study, we developed a computational approach that integrates copy number alteration, gene expression, and a protein interaction network of 73 basal breast cancer samples. 2509 prognostic genes harboring a copy number alteration were identified using survival analysis, and a protein–protein interaction network considering the direct interactions was created. Each patient was described by a specific combination of seven altered hub proteins that fully characterize the 73 basal breast cancer patients. We suggested the optimal combination therapy for each patient considering drug–protein interactions. Our approach is able to confirm well-known cancer related genes and suggest novel potential drug target genes. In conclusion, we presented a new computational approach in breast cancer to deal with the intra-tumor heterogeneity towards personalized cancer therapy.

scholarly journals Chromosomal copy number heterogeneity predicts survival rates across cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erik van Dijk ◽  
Tom van den Bosch ◽  
Kristiaan J. Lenos ◽  
Khalid El Makrini ◽  
Lisanne E. Nijman ◽  
...  
Keyword(s):  
Copy Number ◽  
Cancer Survival ◽  
Survival Rates ◽  
Cancer Prognosis ◽  
Disease Outcomes ◽  
Distinct Disease ◽  
Cancer Types ◽  
Chromosomal Copy Number ◽  
Chromosomal Copy ◽  
Pan Cancer

AbstractSurvival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

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