Clinical Oncology

[The use of NGS in oncology in diagnostic setting]

BECSÁGH Péter

DECEMBER 10, 2018

Clinical Oncology - 2018;5(04)

[Today the information could be the basis of further development by collecting, saving, structuring and analyzing them. Inside the living organism and inside viruses the biochemical storage system was evolved. The linear coding inside macromolecular structures could create and store a series of building block combinations along the chain structure. Those chemical structures are the so called information coding macromolecules, for example, the polypeptides and nucleic acids. Analysis of the genetically coded functionalities of tumor cells has a great impact in the oncological setting. The connected functions of inherited or acquired alterations inside the tumor cell clones are the main contributors of tumor evolution and surviving, although provide a way to target possible mechanism and touch points. Today the oncodiagnostic use of next generation sequencing technology focus on tumor evolution and tumor surviving connected gene set analysis. This kind of gene panel analysis connected to NGS technology is enough enforced - enforced enough - to reach the diagnostic level, but one still need to take care about the quality and standardization to meet the IVD conditions.]

COMMENTS

0 comments

Further articles in this publication

Clinical Oncology

[News from the World]

Clinical Oncology

[Foreword]

A szerkesztők

Clinical Oncology

[Treatment of head and neck cancer]

KATONA Csilla, LANDHERR László

[Head and neck cancers cause worldwide a signifi cant problem in health care systems. Despite great advances in therapeutic modalities its prognosis has not changed in the past few decades. It is mainly caused by classical risk factors, like alcohol consumption and smoking, but in a signifi cant number of oropharyngeal cancers HPV infection plays a major role, which is associated with a new patient group characterized by a much better prognosis and therapeutic response. In the diagnostic phase staging examinations (CT scan, MRI, FDG-PET) are also involved which are necessary to multidisciplinary decision making. It can be largely infl uenced by the patient’s preference. The therapy is based on multimodality approach; surgery, radiotherapy, chemoirradiation, chemotherapy and the combination of these are used in early or locally advanced tumours. Targeted agents like EGFR inhibitors are partly used in the recurrent/metastatic setting or in combination with radiotherapy. Immun checkpoint inhibitors are new therapeutic options for pretreated, recurrent/metastatic patients and their role is under investigation in earlier therapeutic lines. Several clinical trials aim treatment desintensifi cation strategies in HPV positive tumours. Molecular genetic tests try to defi ne subgroups of patients to plan individualized treatment. Regarding the signifi cant functional and aesthetic damage of both disease and treatment, supportive care and rehabilitation are of great importance.]

Clinical Oncology

[PI3K–AKT–mTOR pathway as a therapeutic target]

KOPPER László

[The PI3K-AKT-mTOR is one of the most busy signalling pathway, accepting and sending the message to the effector compartment. The pathway is very complex with activators (see the name), and inhibitors, as PTEN. Depending of the cell type this pathway participates in almost all functions of a given cell. The members of the pathway may have genetic failures, as a consequence, the risk for the development of different diseases, including cancer is high. Therefore it is logical to produce drugs to inhibit the dysregulated function. Unfortunately, despite the promising preclinical effectivity, so far only 4 drugs can be used to treat cancer patients. There are some hypothesis for the in effectivity, e.g. no useful marker for patient selection, high toxicity, false drivers for targeting. What is sure, combination therapy is much better than monotherapy]

Clinical Oncology

[Gene-expression profiles in adjuvant treatment of early breast cancer]

PAJKOS Gábor

[Breast cancer is a heterogeneous disease with different subtypes having a distinct biological, molecular, and clinical course. Assessments of standard clinical and pathological features have traditionally been used to determine the use of adjuvant systemic therapy in early-stage breast cancer; however, the ability to identify those who will benefi t from adjuvant chemotherapy remains a challenge, leading to over treatment of some patients. Risk stratifi cation of patients with early stage breast cancer may support adjuvant chemotherapy decision-making. This review details the development and validation of seven multi-gene classifi ers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test’s analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use.]

All articles in the issue

Related contents

Lege Artis Medicinae

[MOLECULAR DIAGNOSTICS OF EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER]

TÍMÁR József, OSTOROS Gyula

[One of the most useful markers of non-small cell lung cancer is epidermal growth factor receptor (EGFR) protein expression. Recently it was found that the EGFR gene may be amplified or mutated in non-small cell lung cancer rendering this gene product an ideal target for therapy. The introduction of molecularly targeted therapy into the clinical practice represents a milestone in the management of non-small cell lung cancer. However, our knowledge on the prognostic and predictive factors that will define the efficiency of anti-EGFR therapy is limited. In clinical practice, some common patient and disease features (e. g., smoking habit, gender, histological type) are still more dependable predictors than the fine molecular properties that may directly affect therapeutic response. The indication of anti-EGFR therapy in Hungary is based on the immunohistochemical detection of the EGFR protein, therefore, it is important that these tests are performed as reliably as possible. On the other hand, mutations in the EGFR gene may render the tumour resistant or, in contrary, especially sensitive to EGFR inhibitor therapy. The sequence of the diagnostic steps to define the genotype and phenotype of non-small cell lung cancer has a great importance in terms of cost-efficiency of the therapy.]

Clinical Oncology

[Molecular profi les in therapeutic strategy]

PETÁK István, SCHWAB Richárd

[In 2013, 10 years after the completion of the human genome, the cancer genome project has identifi ed almost all possible cancer genes, which could be responsible for the malignant transformation and progression. These genes are called „driver” genes, and the pathogenic mutations to be „driver” mutations. The census of „driver genes” in 2013 counted 138 genes and 1.5 million mutations. The situation is further complicated by the fact that up to 8 „driver” gene can be activated simultaneously in the same tumor, furthermore, the profi le may change during tumor growth and metastatization. 2013 was a turning point also because several targeted therapies were registered. Currently there are about 30 targeted drugs in clinical use and more than 200 targeted compounds in clinical development. This means that in 3-4 years the number of drugs will at least double. Most of the current patients can only access these compounds in clinical trials. But, patient already benefi t signifi cantly more even from phase I clinical trials, if they are selected based on the molecular profi le of the tumor. Fortunately, the advancements of next generation sequencing technologies provide the opportunity to identify all „driver” genes, - the whole molecular profi le, - in the patient’s tumor for the cost of one month targeted therapy. But the information generated can be only used in clinical practice if the results are processed by „molecular info-bionics”.]

Hungarian Radiology

[Current questions of quality assurance in diagnostic radiology in the light of a visit to England]

PORUBSZKY Tamás, GICZI Ferenc, BALLAY László, PELLET Sándor

[Physical-technical aspects of quality assurance in diagnostic radiology, because of its dependence on technology are of an extraordinary importance. The intention of Hungary to join EU makes at least the decrease of our lag in this respect unavoidable. Ministerial order 31/2001 (X. 3.) EüM which already came into force requires quality assurance in diagnostic radiology explicitly. This paper starts with definition of basic concepts, then outlooks shortly the history and present international situation of quality assurance in diagnostic radiology. We review preliminaries and the present situation in Hungary, including results of the National Patient Dose Assessment Programme till now. We think that the most efficient help to the initial steps of quality assurance in diagnostic radiology in Hungary may be the appropriate adaptation of experiences of the leading countries. Therefore we review experiences of one of the authors gained during visiting three medical physics centres in England in details. The following topics are discussed: legal requirements, types and levels of measurements, organizational problems, practical evaluation of measurements (including criteria of discarding equipment), patient dosimetry, personal dosimetry, mammography research, instrumentation of the radiology departments, calibration of measuring devices, questions of the so-called type testing and radiation protection training of workers.]

Lege Artis Medicinae

[ALTERATIONS IN MYOCARDIAL CONTRACTILE PROTEIN COMPOSITION IN DIASTOLIC HEART FAILURE]

PAPP Zoltán, BORBÉLY Attila, ÉDES István

[Disturbances in ventricular relaxation may lead to the development of diastolic heart failure. The analysis of left ventricular endomyocardial biopsy specimens may help understand the underlying structural and functional changes. Such analyses have lead to the recognition that at the optimal sarcomere length of the Frank- Starling mechanism (i.e., at 2.2 μm), passive force values of the cardiomyocytes are significantly higher in individuals with diastolic heart failure than in healthy controls. As a probable explanation to this finding, increased expression of the stiffer N2B isoform of the myofilamental titin protein, at the expense of the more elastic N2BA titin isoform, has been recognized. Moreover, decreased phosphorylation of the contractile proteins was also suggested to contribute to the development of diastolic heart failure. These changes together, and along with an increase in extracellular collagen content, may greatly contribute to the relaxation disturbance observed in diastolic heart failure.]

Clinical Oncology

[Diagnosis and therapy of childhood brain tumors – an update]

GARAMI Miklós

[Childhood cancers are rare disorders. The average annual age-standardized incidence is 149/1000000 (0-14 yrs). Diagnosis of childhood brain tumors, despite the specifi c localization and advanced imaging techniques can cause diffi culties. In recent years, due to better early recognition, number of surgically removable brain tumors is increasing. Early detection of the disease (clinical knowledge), use of modern imaging (fMRI) techniques and detection of characteristic molecular lesions allow up-to-date diagnosis and successful treatments. These approaches provide the basis for risk-adapted personalized treatment options]