Clinical Oncology

[Microsatellites act as „seismographs” of the genome]

SÜKÖSD Farkas1

JUNE 30, 2021

Clinical Oncology - 2021;8(2)

[Short non-protein-coding repetitive regions consisting of 1-6 bp sequences are called microsatellites. Failure in DNA polymerase activity during replication may lead to an increase or reduction in the number of these repeats. Generally, these microsatellite number variations are corrected via the DNA repair machinery; if not, the alterations are transmitted to the progeny, which is also indicated by the elevated mutation rate in the offspring. Microsatellite instability (MSI) can also cause reading-frame problems, and this can lead to elevated expression of foreign antigens in tumors, promising an enhanced efficacy of the anti-tumour immune response. Thus, MSI indicates not only genetic instability but also an increased efficacy of immune checkpoint inhibitors. Various tools such as PCR-based techniques or immunohistochemical methods have been developed to confirm MSI and to examine the functionality of the DNA repair mechanisms in these patients. Additionally, the recent technology also allows us to examine of microsatellites by using next-generation sequencing or artificial intelligence-based image analysis methods. In this review, we summarize recent methodologies and the clinical significance of MSI analysis. ]

AFFILIATIONS

  1. Szegedi Tudományegyetem, Patológiai Intézet, Szeged

COMMENTS

0 comments

Further articles in this publication

Clinical Oncology

[Relevance of adrenal insufficiency in the management of oncological patients]

IGAZ Péter

[Adrenal insufficiency has a complex relevance in oncology. On one hand, malignant tumors warranting treatment might develop in patients suffering from adrenal insufficiency, on the other hand, adrenal insufficiency might appear due to the progression of malignant tumor or to its therapy. During the progression of oncological disease, bilateral adrenal or very rarely pituitary metastases could result in adrenal insufficiency. Novel immune-checkpoint inhibitors, opioids and long-term glucocorticoid treatment can all lead to adrenal insufficiency. It is very important to recognize and to know the treatment of adrenal insufficiency, as failure of treating adrenal insufficiency might be related to severe, even fatal consequences. In this review, these clinically relevant fields are presented.]

Clinical Oncology

[The role of next-generation sequencing in clinival oncology]

KOTMAYER Lili, BÖDÖR Csaba

[Over the past decade next-generation sequencing has led to the in-depth understanding of the molecular background and driving mechanisms in most types of cancer. Parallel to the technological advances, novel targeted therapies have become available for oncology patients. As a result of this process, molecular diagnostics is now one of the main cornerstones of precision medicine with predictive biomarkers aiding patient care in oncology. In addition to standard monogenic testings, recently multigene testing methods based on next-generation sequencing came into view, supporting targeted therapeutic decisions and personalized medicine. In this review, we aim to depict the most important professional aspects related to the reasonable application of next-generation sequencing and the interpretation of its results.]

Clinical Oncology

[Combining angiogenesis- and checkpoint-inhibitors to potentiate each other’s effects]

PIKÓ Béla, BASSAM Ali, MARIK László

[Both, the inhibition of angiogenesis and the influence of immune-mediated processes play significantly growing role in non-surgical treatment of tumors. Neoangiogenesis of neoplasmas adversely affects the function of the immune system, so its inhibition enhances the action of T-lymphocytes and other factors that support their function, favorably affects the microenvironment of the tumor, while treatment with immune signaling sites helps to normalize the vascular system. Influencing those two targeting points together may have a beneficial effect. Authors present that the combined use of agents having those two targets in renal cell carcinoma, melanoma malignum, non-small cell lung cancer, colorectal cancer, hepatocellular and breast cancer noting that successful phase III studies have been performed predominantly in clear cell (or tumor that also contains a clear cell component) carcinomas. The authors emphasize that immunotherapy usually requires the detection of susceptibility-predicting parameters (corresponding PD-L1, MSI-H, dMMR, TMB-H) and that registered indications should be considered in addition to the therapeutic philosophy of tumor agnostic treatment.]

Clinical Oncology

[Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine]

CASOLINO R, BRACONI C, MALLEO G, PAIELLA S, BASSI G, MILELLA M, DREYER S B, FROELING FE M, CHANG D K, BIANKIN A V, GOLAN T

[Summary – This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of ‘all-comer’ treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality.]

Clinical Oncology

[EMDR therapy in the treatment of oncology patients]

HAVELKA Judit

[The diagnosis and treatment of a life-threatening disease such as cancer involves exposure to psychological and physical stress and may constitute a traumatic experience for most people. Abnormal adaptation of neurobiological systems to the stress following experienced trauma, furthermore, individual fac­tors such as previous traumas may also play a role in PTSD development. In the context of oncology, there is a specific need to develop better tools for psychological assessment, that address cancer-related stressors. It is hypothesized that eye movement desensitization and reprocessing (EMDR) therapy promotes the elicitation of the innate self-healing capacity, the natural healing process of the immune system and adaptive information reprocessing. The EMDR therapeutic intervention with oncological patients aims to repair the psychic balance, empower resilience factors and to allow the processing of traumatic disease-related experiences.]

All articles in the issue

Related contents

Lege Artis Medicinae

[Human genome project]

SASVÁRI-SZÉKELY Mária

[The main goal of the Human Genom Project is to reveal the complete structure of the human DNA, involving the sequence determination of the three billion basepairs. The program was launched in 1990, executed in laboratories of the public sector in several countries. Results of this project are made public on the Internet. In 1998 a private sector company, Celera, was founded with the same goal. In 2001 both projects announced the accomplishment of the first draft of the Human Genome. A whole issue of Nature and Science magazine was devoted to present the first results of their findings. According to the results less than one percent of the genetic information is transcribed to proteins. The estimated number of genes was also lower than expected (30-40 thousand, which number recently increased to 40-60 thousand). Based on these findings, human complexity should be ascribed to the variability of the information units (domains) rather than to the number of genes. Once the complete sequence of the humane genome is accomplished, the ’pre-genomic era’ will be over and the ’post-genomic era’ will begin, dealing with understanding the genetic information, annotating the genes and mapping the genetic variability of people.]

Clinical Neuroscience

[Event-related potentials and clinical symptoms in schizophrenia]

DOMJÁN Nóra, CSIFCSÁK Gábor, JANKA Zoltán

[The investigation of schizophrenia’s aetiology and pathomechanism is of high importance in neurosciences. In the recent decades, analyzing event-related potentials have proven to be useful to reveal the neuropsychological dysfunctions in schizophrenia. Even the very early stages of auditory stimulus processing are impaired in this disorder; this might contribute to the experience of auditory hallucinations. The present review summarizes the recent literature on the relationship between auditory hallucinations and event-related potentials. Due to the dysfunction of early auditory sensory processing, patients with schizophrenia are not able to locate the source of stimuli and to allocate their attention appropriately. These deficits might lead to auditory hallucinations and problems with daily functioning. Studies involving high risk groups may provide tools for screening and early interventions; thus improving the prognosis of schizophrenia. ]

Lege Artis Medicinae

[TREATMENT OF HYPERTENSION - RECOMMENDATIONS FOR THE PRACTICE]

PÁLL Dénes

[Hypertension is one of the most common diseases with a prevalence of over 25%. Despite of the availability of modern therapeutic options, the proportion of well-controlled patients is low. Before starting the treatment of patients with hypertension, it is essential to assess cardiovascular risk factors, co-morbidities and damages to target organs, in addition to repeated blood pressure measurements. The author first reviews the non-pharmacological treatment options of hypertension, then summarizes the most important characteristics of first-line antihypertensive agents (diuretics, beta-receptor blockers, calcium channel antagonists, angiotensin converting enzyme inhibitors, angiotensin receptor blockers). Considering the complex pathomechanism of essential hypertension, the author details the advantages and options of combined antihypertensive therapy, touching on the combinations recommended in special conditions. The metabolic effects and side-effects of antihypertensive agents, which have recently gained increased significance, are also discussed. Modern hypertension care is aimed at maximally decreasing cardiovascular morbidity and mortality, and improving the patient's quality of life. Maximum decrease of cardiovascular risk not only involves proper blood pressure control, but also aggressive fight against other risk factors (e.g., diabetes, dyslipidaemia, smoking) and treatment of target organ damages and comorbidities.]