التفاصيل البيبلوغرافية
| العنوان: |
Genomic landscape of cell-free DNA in patients with colorectal cancer |
| المؤلفون: |
Rebecca J. Nagy, W. Michael Korn, Amir Ali Talasaz, Richard B. Lanman, Funda Meric-Bernstam, Kimberly C. Banks, Donna Niedzwiecki, Leanne G. Ahronian, John H. Strickler, Chloe E. Atreya, Allan Andresson Lima Pereira, Jonathan M. Loree, Scott Kopetz, Matthew McKinney, Ryan B. Corcoran, Igor F. Tsigelny, Aparna Raj Parikh |
| المصدر: |
Cancer discovery, vol 8, iss 2 |
| سنة النشر: |
2017 |
| مصطلحات موضوعية: |
0301 basic medicine, Colorectal cancer, Sequencing data, Oncology and Carcinogenesis, Article, Clonal Evolution, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Genetics, Biomarkers, Tumor, 2.1 Biological and endogenous factors, Humans, In patient, Genetic Testing, Liquid biopsy, Aetiology, Cancer, Tumor, biology, Human Genome, DNA, DNA, Neoplasm, Genomics, medicine.disease, Colo-Rectal Cancer, ErbB Receptors, 030104 developmental biology, Good Health and Well Being, Oncology, Cell-free fetal DNA, Ectodomain, chemistry, 030220 oncology & carcinogenesis, Mutation, biology.protein, Cancer research, Neoplasm, Antibody, Digestive Diseases, Colorectal Neoplasms, Cell-Free Nucleic Acids, Biomarkers, Genome-Wide Association Study |
| الوصف: |
“Liquid biopsy” approaches analyzing cell-free DNA (cfDNA) from the blood of patients with cancer are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cohorts of patients with cancer can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based colorectal cancer sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range, 1–13; median, 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biological insights. Significance: This study provides one of the first examples of how large-scale genomic profiling of cfDNA from patients with colorectal cancer can detect genomic alterations at frequencies comparable to those observed by direct tumor sequencing. Sequencing of cfDNA also generated insights into tumor heterogeneity and therapeutic resistance and identified novel EGFR ectodomain mutations. Cancer Discov; 8(2); 164–73. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 127 |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6bee5983b98967c2d4b0a913e8c3d1ab
https://europepmc.org/articles/PMC5809260/ |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....6bee5983b98967c2d4b0a913e8c3d1ab |
| قاعدة البيانات: |
OpenAIRE |