Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing
| العنوان: | Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing |
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| المؤلفون: | Paul T. Fanta, David Piccioni, In Sil Choi, Razelle Kurzrock, Lyudmila Bazhenova, Shumei Kato, Maria Schwaederle, Richard B. Lanman, Ranajoy Chattopadhyay, Sadakatsu Ikeda, Kimberly C. Banks, Amir Ali Talasaz |
| المصدر: | Cancer research, vol 77, iss 19 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, medicine.disease_cause, Bioinformatics, 0302 clinical medicine, Neoplasms, 80 and over, Young adult, Child, Cancer, Aged, 80 and over, Mutation, Tumor, High-Throughput Nucleotide Sequencing, DNA, Neoplasm, Genomics, Middle Aged, Child, Preschool, 030220 oncology & carcinogenesis, Cohort, Female, KRAS, Biotechnology, Adult, medicine.medical_specialty, Adolescent, Oncology and Carcinogenesis, Biology, Article, DNA sequencing, Young Adult, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, Genetics, Biomarkers, Tumor, medicine, Humans, Oncology & Carcinogenesis, Preschool, Aged, Retrospective Studies, Human Genome, Retrospective cohort study, DNA, Precision medicine, medicine.disease, Good Health and Well Being, 030104 developmental biology, Neoplasm, human activities, Biomarkers |
| الوصف: | Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [N = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in TP53 (32.5% of patients), EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, 30.7% (TP53), 7.6% (EGFR), 12.2% (KRAS), and 7.7% (PIK3CA). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis (P = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. Cancer Res; 77(19); 5419–27. ©2017 AACR. |
| وصف الملف: | application/pdf |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-17-0885 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1eba3a608cbbc1748abf629e3cb76868 https://doi.org/10.1158/0008-5472.can-17-0885 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1eba3a608cbbc1748abf629e3cb76868 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/0008-5472.can-17-0885 |