المؤلفون: Li-Dong Wang, Jianshan Mao, Weiting Ge, Hanguang Hu, Wen Cai, Dehao Wu, Wangxiong Hu, Shu Zheng

المصدر: Cancer Medicine

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, colorectal cancer, Genetic Heterogeneity, Young Adult, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Internal medicine, Cancer genome, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Radiology, Nuclear Medicine and imaging, Pooled data, Age of Onset, Poly-ADP-Ribose Binding Proteins, Aged, Neoplasm Staging, Original Research, Aged, 80 and over, business.industry, driver mutation, Early disease, Clinical Cancer Research, DNA Polymerase II, Middle Aged, medicine.disease, Phenotype, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, POLE, Cohort, Female, heterogeneity, Colorectal Neoplasms, clinical patterns, business

الوصف: POLE mutations, which lead to an ultramutated phenotype in colorectal cancer (CRC), have been reported as a promising marker in immunotherapy. We performed sequencing of CRC cases in Zhejiang University (ZJU) and extracted obtainable data from recently published results, including The Cancer Genome Atlas (TCGA), Japanese studies and clinical trials, to present clinical patterns of POLE driver‐mutated CRC and reveal its heterogeneity. The rate of somatic POLE driver mutations has been reported as 2.60% (ZJU cohort), 1.50% (TCGA cohort), 1.00% (Japan cohort), and 1.00% (Lancet cohort). POLE driver mutations show a clearly increased mutation burden (mean TMB: 217.98 mut/Mb in ZJU; 203.13 mut/Mb in TCGA). Based on pooled data, more than 70.00% of patients with POLE driver mutations were diagnosed before they were 55 years old and at an early disease stage (Stage 0–II >70.00%), and more than 70.00% were male. Among Asian patients, 68.40% developed POLE driver mutations in the left‐side colon, whereas 64.00% of non‐Asian patients developed them in the right‐side colon (p
POLE could be a promising marker for immunotherapy, and its heterogeneity should not be ignored. Here we present the clinical patterns and heterogeneity of POLE driver mutations so that investigators and physicians will be better equipped to design clinical trials and analyze their data.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8f4213af4f9ceb6c9080d702e9c787fTest
https://doi.org/10.1002/cam4.3579Test

المؤلفون: Jun Ouyang, Weirong Fan, Xueli Zhang, Rong Zhang, Yuan Ren, Zhigang Zhang, Lining Cui, Tianjiao Luo, Fangliang Xing, Xuefeng Bai, Xin Xing, Huan Yi, Fengmian Wang, Cancan Zhang, Linyan Zhu, Qin Yang, Jianping Qiu, Pengcheng Jiang

المصدر: Neoplasia (New York, N.Y.)
Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 9, Pp 399-430 (2020)

مصطلحات موضوعية: Oncology, 0301 basic medicine, Cancer Research, ARID1A, medicine.disease_cause, 0302 clinical medicine, Tumor Cells, Cultured, Exome sequencing, Ovarian clear cell carcinomas, Ovarian Neoplasms, Medical record, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Clear cell carcinoma, MAGEE1, Female, KRAS, Target sequencing, Adult, medicine.medical_specialty, Original article, Biology, Malignancy, lcsh:RC254-282, Chromatin remodeling, 03 medical and health sciences, Asian People, Internal medicine, Exome Sequencing, medicine, Biomarkers, Tumor, PTEN, Humans, PI3K/AKT/mTOR pathway, Aged, Retrospective Studies, business.industry, Whole exome sequencing, Cancer, Driver mutation, medicine.disease, 030104 developmental biology, Case-Control Studies, Mutation, Cancer research, biology.protein, business, Biomedical sciences, Adenocarcinoma, Clear Cell, Follow-Up Studies

الوصف: Background: Little is known about the genetic alterations characteristic of ovarian clear cell carcinoma (OCCC). Our aim was to identify targetable genomic alterations in this type of cancer. Methods: Forty-two OCCC formalin-fixed, paraffin-embedded (FFPE) tissue samples were analyzed by whole-exome sequencing (WES), and 74 FFPE tissue samples underwent targeted sequencing (TS) to confirm the relevant driver mutations. Cell proliferation was assessed by cell counting kit-8 (CCK8) assays. Findings: In the 42 samples, ARID1A (64.3%) and PIK3CA (28.5%) were frequently mutated, as were PPP2R1A (11.9%), PTEN (7.1%) and KRAS (4.8%), which have been reported in previous OCCC studies. We also detected mutations in MUC4 (28.6%), MAGEE1 (19%), and ARID3A (16.7%); associations with these genes have not been previously reported. The functional protein-activated pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 83% of OCCCs and with chromatin remodeling in 71% of OCCCs. Patients with alterations in MAGEE1 (64% in the targeted sequencing cohort) had worse clinical outcomes (log-rank p < 0.05). A functional study revealed that two MAGEE1 mutants, one lacking two MAGE domains and the other containing two MAGE domains, significantly decreased the proliferative capacity of OCCC cells. Funding: We successfully identified novel genetic alterations in OCCC using whole-exome sequencing and targeted sequencing of OCCC patient samples and potential therapeutic targets for the treatment of this malignancy. Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The use of samples and medical records was approved by the research ethics committees of Shanghai University of Medicine & Health Sciences Affiliated with Sixth People’s Hospital South Campus (approval number: 2017-KY-01), Fujian Provincial Maternity and Children's Hospital (approval number: 2017049), Nanjing Medical University Affiliated with Changzhou Maternal and Child Health Care Hospital (approval number: 2017005), Nanjing Medical University Affiliated with Changzhou No. 2 People’s Hospital (approval number: 2016-017-01), and Nanjing Medical University Affiliated with Suzhou Municipal Hospital (approval number: L2017003).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b91d898e4feb659a83c42f0618a45b8dTest
http://europepmc.org/articles/PMC7341065Test

المؤلفون: Thüsen J.H. von der, Melinda A. Pruis, A-M.C. Dingemans, Willemina R. R. Geurts-Giele, Isabelle C. Meijssen, W. Dinjens, Marthe S. Paats, Hendrikus J. Dubbink, Martijn P. Lolkema, Joachim G.J.V. Aerts

المساهمون: Medical Oncology, Pulmonary Medicine, Pathology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9)

المصدر: Lung Cancer, 140, 46-54. Elsevier Ireland Ltd

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, medicine.medical_treatment, sarcomatoid carcinoma, amplification, medicine.disease_cause, Targeted therapy, Exon, 0302 clinical medicine, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, diagnostics, CRIZOTINIB, met exon 14 skipping, Aged, 80 and over, Mutation, High-Throughput Nucleotide Sequencing, DNA, Neoplasm, Exons, Middle Aged, Proto-Oncogene Proteins c-met, Amplicon, Prognosis, MET Exon 14 Skipping Mutation, Survival Rate, 030220 oncology & carcinogenesis, Female, medicine.drug, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Resistance against cMET inhibition, INHIBITION, Adenocarcinoma of Lung, PATIENT, DNA sequencing, target, resistance, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Next generation sequencing, met inhibitor, Biomarkers, Tumor, medicine, Humans, Lung cancer, Protein Kinase Inhibitors, Aged, Retrospective Studies, Crizotinib, Diagnostic Tests, Routine, business.industry, driver mutation, medicine.disease, 030104 developmental biology, business, Follow-Up Studies

الوصف: Objectives The oncogenic MET exon 14 skipping mutation (METex14del) is described to drive 1.3 %–5.7 % of non-small-cell lung cancer (NSCLC) and multiple studies with cMET inhibitors show promising clinical responses. RNA-based analysis seems most optimal for METex14del detection, however, acquiring sufficient RNA material is often problematic. An alternative is DNA-based analysis, but commercially available DNA-based panels only detect up to 63 % of known METex14del alterations. The goal of this study is to describe an optimized DNA-based diagnostic test for METex14del in NSCLC, including clinical features and follow-up of patients treated with cMET-targeted therapy and consequent resistance mechanisms. Material and methods Routinely processed diagnostic pathology non-squamous NSCLC specimens were investigated by a custom-made DNA-based targeted amplicon-based next generation sequencing (NGS) panel, which includes 4 amplicons for METex14del detection. Retrospectively, histopathological characteristics and clinical follow up were investigated for advanced non-squamous NSCLC with METex14del. Results In silico analysis showed that our NGS panel is able to detect 96 % of reported METex14 alterations. METex14del was found in 2 % of patients with non-squamous NSCLC tested for therapeutic purposes. In total, from May 2015 - Sep 2018, METex14del was found in 46 patients. Thirty-six of these patients had advanced non-squamous NSCLC, they were predominantly elderly (76.5 years [53–90]), male (25/36) and (ex)-smokers (23/36). Five patients received treatment with crizotinib (Pfizer Oncology), in a named patient based program, disease control was achieved for 4/5 patients (3 partial responses, 1 stable disease) and one patient had a mixed response. Two patients developed a MET D1228N mutation during crizotinib treatment, inducing a resistance mechanism to crizotinib. Conclusions This study shows that METex14del can be reliably detected by routine DNA NGS analysis. Although a small cohort, patients responded well to targeted treatment, underlining the need for routine testing of METex14del in advanced non-squamous NSCLC to guarantee optimal personalized treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::057efac93cf37bf55ac4d294f4b0aedfTest
https://doi.org/10.1016/j.lungcan.2019.11.010Test

المؤلفون: María Teresa Rodrigo-Calvo, Roberto Chalela, Karys Khilzi, Beatriz Bellosillo, Raquel Longarón, Joaquim Gea, Albert Sánchez-Font, Jose Gregorio González-García, Clara Martín-Ontiyuelo, Víctor Curull

المصدر: Pathology and Oncology Research
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona

مصطلحات موضوعية: Male, Cancer Research, Lung Neoplasms, 030204 cardiovascular system & hematology, medicine.disease_cause, EGFR–epidermal growth factor receptor, Exon, 0302 clinical medicine, adenocacinoma lung, Aged, 80 and over, 05 social sciences, General Medicine, Middle Aged, Brief Research Report, Prognosis, Primary tumor, ErbB Receptors, Society Journal Archive, medicine.anatomical_structure, Oncology, Adenocarcinoma, Female, KRAS, Adenocarcinoma of Lung, Pathology and Forensic Medicine, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0502 economics and business, Parenchyma, medicine, Biomarkers, Tumor, Humans, Parenchymal Tissue, Aged, EGFR-epidermal growth factor receptor, Lung, business.industry, driver mutation, Wild type, Driver mutation, medicine.disease, respiratory tract diseases, Case-Control Studies, Mutation, Cancer research, Adenocacinoma lung, 050211 marketing, business, Carcinogenesis, Follow-Up Studies

الوصف: The acquisition of driver mutations in non-tumoral cells appears to be very important during the carcinogenesis of adenocarcinoma (ADC). Recent studies suggest that cancer-related mutations may not necessarily be present only in malignant cells, but also in histologically “healthy cells”.Objective: to demonstrate the presence of EGFR or KRAS mutations in non-tumoral lung cells in subjects with ADC and negative mutational status.Results: mutations in EGFR or KRAS oncogenes were identified in the normal lung in 9.7% of the subjects. Exon 21 substitution L858R in EGFR was detected in two cases while the exon 19 deletion E746-A750 in the EGFR, the G12C and G12D substitutions in the KRAS were detected once. One patient presented three different mutations in the normal lung parenchyma (EGFR_L858R, KRAS_G12C and KRAS_G12D). The negative-mutation status of the tumor and the mutations detected in the “normal lung” were confirmed using highly sensitive and specific TaqMan PCR (CAST-PCR). No differences were found in terms of progression, progression-free survival or overall survival during the 18 months follow-up.Conclusions: These results confirm the presence of driver mutations in the histologically normal lung parenchyma cells in the absence of mutations coexisting with the primary tumor.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c957cf5e27bfd158703fa17ee259ff12Test
https://ddd.uab.cat/record/248155Test

المؤلفون: Yusuke Shinozaki, Kei Morikawa, Takeo Inoue, Masamichi Mineshita, Hiroki Nishine, Masahiro Iinuma

المصدر: Therapeutic Advances in Medical Oncology
Therapeutic Advances in Medical Oncology, Vol 13 (2021)

مصطلحات موضوعية: Metastatic lesions, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Mutually exclusive events, EGFR-mutant lung cancer, BRAF-mutant lung cancer, Oncology, double driver mutation, Mutation (genetic algorithm), medicine, Cancer research, Adenocarcinoma, case report, business, Lung cancer, Gene, RC254-282

الوصف: Driver mutations in lung cancer have been generally considered mutually exclusive; however, multiple gene screenings have recently become mainstream. Therefore, it is not uncommon to identify two or more mutations at first diagnosis, making it difficult to determine which tyrosine kinase inhibitor to administer. A 69-year-old woman complaining of back pain was diagnosed with adenocarcinoma T4N3M1c, stage IVB. Although PCR mutation test detected exon21 L858R point mutation by bronchoscopic sample, the therapeutic effect of afatinib was poor. Subsequently, next-generation sequencing (NGS) panel test of a metastasized bone specimen confirmed BRAF V600E. Furthermore, high sensitivity NGS panel system found the gene mutation allele frequency was higher for BRAF V600E than EGFR exon21 L858R for both primary lung tissue and the metastasized specimen. Subsequent BRAF/MEK inhibitor administration showed a remarkable treatment effect. When two or more driver mutations are detected in lung cancer, confirming the allelic frequency of the mutant gene might be useful in selecting more effective agents for front-line treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9a53351b576bc3509b18628d6be5682Test
http://europepmc.org/articles/PMC8544759Test

المؤلفون: Corina van den Hurk, Annemarie Becker-Commissaris, Vashti N. M. F. Tromp, Iris Walraven, Nicole E Billingy

المساهمون: Pulmonary medicine, Clinical pharmacology and pharmacy, CCA - Cancer Treatment and quality of life, Ophthalmology, APH - Quality of Care, APH - Aging & Later Life

المصدر: Cancers
Volume 13
Issue 17
Cancers, 13(17):4282. Multidisciplinary Digital Publishing Institute (MDPI)
Cancers, 13, 17
Billingy, N E, Tromp, V N M F, van den Hurk, C J G, Becker-Commissaris, A & Walraven, I 2021, ' Health-Related Quality of Life and Survival in Metastasized Non-Small Cell Lung Cancer Patients with and without a Targetable Driver Mutation ', Cancers, vol. 13, no. 17, 4282 . https://doi.org/10.3390/cancers13174282Test
Cancers, Vol 13, Iss 4282, p 4282 (2021)
Cancers, 13

مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, Article, Gee, All institutes and research themes of the Radboud University Medical Center, Quality of life, Internal medicine, medicine, Lung cancer, Generalized estimating equation, Survival analysis, RC254-282, non-small cell lung cancer, Health related quality of life, business.industry, metastatic lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, humanities, health-related quality of life, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Observational study, Non small cell, business, targetable driver mutation

الوصف: Background: The aim of this study is to compare long-term health-related quality of life (HRQOL) and survival in metastatic NSCLC patients with (M+) and without (M−) a targetable driver mutation. Methods: An observational study was performed within the prospective SYMPRO-lung study (NL7897). HRQOL questionnaires were completed at baseline, 15 weeks, and 6 months. Generalized estimating equations (GEE) were used to assess clinically significant declines in HRQOL (>
10 points) over time. Kaplan–Meier survival curves were plotted for both progression-free survival (PFS) and overall survival (OS). Results: 81 metastatic NSCLC patients were included (M+ patients
16 (20%)). M+ patients had a significantly better global HRQOL (mean difference 12.8, ES 0.61), physical functioning (mean difference 13.4, ES 0.63), and less appetite loss (mean difference 23.1, ES 0.73) at 15 weeks of follow-up compared to M− patients. Patients with a clinically relevant decline in HRQOL at 6 months of follow-up had a significantly shorter PFS (5 months vs. 12 months, p-value <
0.001) and OS (11 months vs. 16 months, p-value 0.002). Conclusions: M− NSCLC patients have less favorable HRQOL over time compared to M+ patients. Furthermore, clinically relevant HRQOL declines over time were significantly associated with worse survival. HRQOL can therefore play an important role in in shaping patients’ expectations of their prognosis.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5214ee4729ef478ba1c5e7c67ee702baTest

المؤلفون: Marco Casciaro, Giovanni Pioggia, Alessandro Tonacci, Alessandro Allegra, Caterina Musolino, Sebastiano Gangemi

المصدر: Antioxidants, Vol 9, Iss 1037, p 1037 (2020)
Antioxidants
Antioxidants 9 (2020). doi:10.3390/antiox9111037
info:cnr-pdr/source/autori:Alessandro Allegra; Giovanni Pioggia; Alessandro Tonacci; Marco Casciaro; Caterina Musolino; Sebastiano Gangemi/titolo:Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR-ABL-Negative Myeloproliferative Neoplasm/doi:10.3390%2Fantiox9111037/rivista:Antioxidants/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:9

مصطلحات موضوعية: 0301 basic medicine, Physiology, Clinical Biochemistry, Inflammation, myelofibrosis, Review, Biochemistry, myeloproliferative neoplasms, thrombotic complication, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, polycythemia vera, Medicine, oxidative stress, Myelofibrosis, Molecular Biology, Driver mutation, Essential thrombocythemia, Myeloproliferative neoplasms, Oxidative stress, ROS, Thrombotic complication, Myeloproliferative neoplasm, Janus kinase 2, biology, essential thrombocythemia, business.industry, driver mutation, lcsh:RM1-950, Cell Biology, medicine.disease, Haematopoiesis, 030104 developmental biology, lcsh:Therapeutics. Pharmacology, inflammation, 030220 oncology & carcinogenesis, Cancer research, biology.protein, medicine.symptom, Stem cell, business

الوصف: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In BCR–ABL1-negative MPNs, the driver mutations include JAK 2, MPL, and CALR. Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9a4a4711eba2611ab805fcebe18fee6Test
https://www.mdpi.com/2076-3921/9/11/1037Test

المؤلفون: Luisa Marracino, Gianluca Campo, Francesca Fortini, Mauro Vaccarezza, Paola Rizzo, Francesco Vieceli Dalla Sega, Veronica Papa

المصدر: Journal of Clinical Medicine, Vol 9, Iss 2480, p 2480 (2020)
Journal of Clinical Medicine

مصطلحات موضوعية: clonal hematopoiesis of indeterminate potential, driver mutation, DNMT3A, TET2, atherosclerosis, clonal hematopoiesis of indeterminate potential, lcsh:Medicine, Context (language use), Review, Disease, 030204 cardiovascular system & hematology, medicine.disease_cause, NO, 03 medical and health sciences, 0302 clinical medicine, medicine, coronary heart disease, 030304 developmental biology, 0303 health sciences, Mutation, TET2, business.industry, lcsh:R, driver mutation, Hematopoietic stem cell, Cancer, General Medicine, medicine.disease, Haematopoiesis, medicine.anatomical_structure, Immunology, DNMT3A, Stem cell, atherosclerosis, business, Indeterminate

الوصف: Some random mutations can confer a selective advantage to a hematopoietic stem cell. As a result, mutated hematopoietic stem cells can give rise to a significant proportion of mutated clones of blood cells. This event is known as “clonal hematopoiesis.” Clonal hematopoiesis is closely associated with age, and carriers show an increased risk of developing blood cancers. Clonal hematopoiesis of indeterminate potential is defined by the presence of clones carrying a mutation associated with a blood neoplasm without obvious hematological malignancies. Unexpectedly, in recent years, it has emerged that clonal hematopoiesis of indeterminate potential carriers also have an increased risk of developing cardiovascular disease. Mechanisms linking clonal hematopoiesis of indeterminate potential to cardiovascular disease are only partially known. Findings in animal models indicate that clonal hematopoiesis of indeterminate potential-related mutations amplify inflammatory responses. Consistently, clinical studies have revealed that clonal hematopoiesis of indeterminate potential carriers display increased levels of inflammatory markers. In this review, we describe progress in our understanding of clonal hematopoiesis in the context of cancer, and we discuss the most recent findings linking clonal hematopoiesis of indeterminate potential and cardiovascular diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecc2ca3e1d13d0a15bfe0a655e8cc014Test
http://hdl.handle.net/11392/2421786Test

المؤلفون: Adnan Akbar, Nirmesh Patel, Ionut Dragomir, Harry W. Clifford, John W. Cassidy, Gianmarco Contino

المساهمون: Dragomir, Ionut [0000-0003-0509-6761], Contino, Gianmarco [0000-0001-5874-0405], Apollo - University of Cambridge Repository

المصدر: Cancers, Vol 13, Iss 2779, p 2779 (2021)
Cancers
Volume 13
Issue 11

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Computer science, Decision tree, pan-cancer, Genomics, Machine learning, computer.software_genre, Article, support vector machines, 03 medical and health sciences, 0302 clinical medicine, k-nearest neighbours, decision tree, Feature (machine learning), multilayer perceptron, RC254-282, business.industry, logistic regression, driver mutation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Precision medicine, Random forest, Support vector machine, Statistical classification, 030104 developmental biology, Oncology, classification, 030220 oncology & carcinogenesis, Multilayer perceptron, extreme gradient boosting, Artificial intelligence, business, computer, random forest

الوصف: Simple Summary Genes dictate the grounds of life by comprising molecular bases which encode proteins. A mutation represents a gene modification that may influence the protein function. Cancer occurs when the mutation triggers uncontrolled cellular growth. Judging by the cancer expansion, mutations labelled as drivers confer a growth advantage, while passengers do not contribute to this augmentation. The aim of this study is methodological, which assesses the usefulness of a classification method for distinguishing between driver and passenger mutations. Based on 51 molecular characteristics of mutations and genes, including 3 novel features, multiple machine learning algorithms were used to determine whether these characteristics biologically represent the driver mutations and how they impact the classification procedure. To test the ability of the present methodology, the same steps were applied to an independent dataset. The results showed that both gene and mutation level characteristics are representative of the driver mutations, and the proposed approach achieved more than 80% accuracy in finding the true type of mutation. The evidence suggests that machine learning methods can be used to gain knowledge from mutational data seeking to deliver more targeted cancer treatment. Abstract Sporadic cancer develops from the accrual of somatic mutations. Out of all small-scale somatic aberrations in coding regions, 95% are base substitutions, with 90% being missense mutations. While multiple studies focused on the importance of this mutation type, a machine learning method based on the number of protein–protein interactions (PPIs) has not been fully explored. This study aims to develop an improved computational method for driver identification, validation and evaluation (DRIVE), which is compared to other methods for assessing its performance. DRIVE aims at distinguishing between driver and passenger mutations using a feature-based learning approach comprising two levels of biological classification for a pan-cancer assessment of somatic mutations. Gene-level features include the maximum number of protein–protein interactions, the biological process and the type of post-translational modifications (PTMs) while mutation-level features are based on pathogenicity scores. Multiple supervised classification algorithms were trained on Genomics Evidence Neoplasia Information Exchange (GENIE) project data and then tested on an independent dataset from The Cancer Genome Atlas (TCGA) study. Finally, the most powerful classifier using DRIVE was evaluated on a benchmark dataset, which showed a better overall performance compared to other state-of-the-art methodologies, however, considerable care must be taken due to the reduced size of the dataset. DRIVE outlines the outstanding potential that multiple levels of a feature-based learning model will play in the future of oncology-based precision medicine.

وصف الملف: application/zip; text/xml; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::424f14e322eaf17edcba8483f856177fTest
https://pubmed.ncbi.nlm.nih.gov/34205004Test

المؤلفون: Shi-Ming Tu

المصدر: Cancers, Vol 13, Iss 674, p 674 (2021)
Cancers

مصطلحات موضوعية: 0301 basic medicine, cancer stem cells, Cancer Research, medicine.medical_treatment, precision medicine, Big data, lcsh:RC254-282, DNA sequencing, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, cancer genome, medicine, Narrative, health care economics and organizations, business.industry, driver mutation, Cancer, Precision medicine, medicine.disease, targeted therapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Data science, Heteroplasmy, humanities, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Perspective, Psychology, business

الوصف: Simple Summary The observation that genetic mutations often do not cause cancer or disease in the phenomena of mosaicism, clonal hematopoiesis of indeterminate potential (CHIP), and heteroplasmy provides us with important clues about the origin and nature of cancer. We should be wary that the cancer genome may lead us astray to the wrong destination on a bad expedition unless we adopt the right cancer theory to elucidate it, and adhere to the proper scientific method to investigate it. Abstract Nowadays, many professionals are sequencing the DNA and studying the cancer genome. However, if the genetic theory of cancer is flawed, our faith in the cancer genome will falter. If gene sequencing is only a tool, we should question what we are making or creating with this tool. When we do not have the right cancer theory at our disposal, we cannot be sure that what we create from the cancer genome is meaningful or useful. In this article, we illustrate that mosaicism, CHIP, and heteroplasmy dispute our traditional perspectives about a genetic origin of cancer and challenge our current narratives about the cancer genome. We caution that when we have the wrong cancer theory, big data can provide poor evidence. Precision medicine may become rather imprecise. Targeted therapy either does not work or work for the wrong reasons. The cancer genome thus becomes a paradox rather than a paradigm.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::647a6e9fc289f135d6ed38a7b9f472cbTest
https://www.mdpi.com/2072-6694/13/4/674Test