Biomarkers in tumors of the central nervous system – a review

Abstract

Until recently, diagnostics of brain tumors were almost solely based on morphology and immunohistochemical stainings for relatively unspecific lineage markers. Although certain molecular markers have been known for longer than a decade (combined loss of chromosome 1p and 19q in oligodendrogliomas), molecular biomarkers were not included in the WHO scheme until 2016. Now, the classification of diffuse gliomas rests on an integration of morphology and molecular results. Also, for many other central nervous system tumor entities, specific diagnostic, prognostic and predictive biomarkers have been detected and continue to emerge. Previously, we considered brain tumors with similar histology to represent a single disease entity. We now realize that histologically identical tumors might show alterations in different molecular pathways, and often represent separate diseases with different natural history and response to treatment. Hence, knowledge about specific biomarkers is of great importance for individualized treatment and follow‐up. In this paper we review the biomarkers that we currently use in the diagnostic work‐up of brain tumors.

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

“…Primary tumors of the Central Nervous System (CNS) are a heterogeneous group of malignancies affecting mainly the brain and, to a lesser extent, spinal cord, sellar region, and cranial and spinal nerves. A recent classification by the World Health Organization (WHO) indicates that different CNS tumor entities or variants are approximately 130 [60]. Glioma is the most common tumor of the brain.…”

“…The molecular pathways involved in CNS tumor formation have been partially elucidated in the last years. However, despite the growing evidence of GOLPH3 involvement in CNS tumor formation, this protein is not yet included in a standard set of their molecular biomarkers [60,61].…”

NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target

“…As a result, diagnostic algorithms are undergoing substantial changes for many tumor types: this molecular revolution has been fully undertaken by the latest 2016 World Health Organization (WHO) classification of central nervous system (CNS) neoplasms, as molecular markers (e.g., IDH1/IDH2 (Isocitrate dehydrogenase 1/2), 1p/19q codeletion, ATRX (transcriptional regulator ATRX), TP53 (tumor protein p53) etc.) have become mandatory for a conclusive diagnosis of many specific tumor entities [6][7][8][9]. Moreover, in the following few years since its publication, the diagnostic/prognostic/predictive importance of many additional molecular traits have been demonstrated and they are now being quickly translated into the routine clinical practice [10][11][12].…”

Predictive Role of Local Cytokine Levels in the Course of Poorly Differentiated Glial Tumors

“…Ген MGMT кодирует фермент MGMT (О 6метилгуанин-ДНК-метилтрансфераза), основная функция которого сводится к репарации поврежденной ДНК. Таким образом, наличие метилирования гена MGMT (или низкий уровень его экспрессии в опухолевых клетках) приводит к снижению активности фермента и закономерному снижению репарационных процессов, что и является основой эффективности терапии алкилирующими агентами и увеличивает медиану выживаемости пациентов [3,4].…”

“…Так, по результатам ряда исследований, общая медиана выживаемости пациентов с ГБ при стандартизированном подходе к лечению при метилировании промотора MGMT составляет 21 месяц, при отсутствии -14 месяцев [3], а при его уровне более 10% отмечена большая восприимчивость к темозоломиду [4].…”