Glioblastoma is the most frequent and aggressive brain tumor in the adult population. Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases. We have tested 124 glioblastoma samples for LOH by microsatellite analysis of the 10q23.3-26.3 region which contains the cancer related genes PTEN, FGFR2, MKI67, and MGMT. Then, a real-time quantitative microsatellite analysis (QuMA) was used to qualitatively estimate the change in copy number of this region in the samples with LOH. LOH was detected in 62.1% of the glioblastoma samples. A total of 64 samples with LOH in this region were examined by QuMA. LOH was attributed to a deletion in 37.5% of cases, and uniparental disomy (UPD) in 25% of cases. In 37.5% of cases, deletion and UPD segments alternated within the region: deletions being more frequent than UPD in its proximal part (encompassing PTEN and FGFR2) and both deletions and UPD occurring at the same frequency in its distal part (MGMT). Thus, we have investigated mechanisms of structural alterations of the chromosome region 10q23.3-26.3 in glioblastoma. In addition to a structural deletion of this region, UPD was identified as a frequent cause of LOH. We resume that more detailed studies of glioblastoma at the molecular genetic level are essential in search for potential markers suitable for predicting the disease outcome and the response to treatment. | I N TR ODU C TI ONGlioblastoma is the most frequent and aggressive brain tumor in the adult population. Glioblastomas account for 80% of primary neoplasms of the central nervous system and are thereby among the most vital problems of neuro-oncology. At the molecular level, glioblastoma has been studied rather comprehensively and is characterized by many genetic and epigenetic alterations, which affect various cancer related genes.1 In spite of the vast data accumulated in the molecular genetics of glioblastoma, only few markers are known to predict the prognosis and response to therapy, the set including abnormal methylation of the MGMT promoter region and IDH1 mutations, which are used in clinical practice.
Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis. Material and method. In P. A. Hertsen Moscow Oncology Research Institute Резюме: Цель. Увеличение выживаемости больных с вторичным поражением головного мозга, а также выявление факторов благоприятного и негативного прогноза. Материалы и методы. В ФГБУ МНИОИ им. П. А. Герцена Минздрава России с 2007 по 2013 гг было пролечено 268 больных с метастазами в головном мозге. Средний возраст составлял 55,8 лет (от 24 до 81 года). Метастазы колоректального рака выявлены в 7,8% случаев, рака лёгкого в 34%, меланомы кожи в 9,3%, рака молочной железы в 26%, рака почки в 11%, без выявленного первичного очага в 4,5%, на другие опухоли приходилось 6,7%. Солитарный метастаз диагностирован у 164 (61,19%) пациента, олигометастазы (2-3)-у 72 (26,87%) больных, множественные метастазы (более 3)-у 32 (11,94%) больных. У 106 (39,55%) больных метастатическое поражение головного мозга было единственным проявлением генерализации процесса. С целью контроля радикальности удаления опухоли у 93 (34,7%) больных использовался метод флуоресцентной навигации (ФД) с препаратом Аласенс. У 66 (24,6%) больных интраоперационно проводился сеанс фотодинамической терапии (ФДТ). В 212 (79,1%) случаях удаление метастаза выполнено тотально, у 55 (20,9%) больных констатировано субтотальное удаление. Результаты. Период наблюдения за больными составил от 3 до 79 месяцев. Медиана выживаемости среди всей группы больных с метастатическим поражением головного мозга составила 12 месяцев. Общая выживаемость достоверно зависела от RPA класса, объёма проведённого послеоперационного лечения, гистологического типа первичной опухоли, количества внутримозговых метастазов и сроках безрецидивного периода. Выводы. Факторами, влияющими на общую выживаемость являются особенности гистологии первичного очага, множественность метастатического поражения, RPA класс и синхронный характер метастазирования. Медиана общей выживаемости больных, не получавших после хирургического лечения иного вида терапии, составила всего 4 месяца. При использовании комбинированного лечения (хирургическое лечение с облучением всего головного мозга) медиана выживаемости составляла 9-10,5 месяцев (в зависимости от метода облучения). При применении лекарственного лечения медиана общей выживаемости составила 11 месяцев. При комплексном лечении показатели выживаемости были наиболее высокими-12 месяцев.
Introduction. Melanoma of the skin has the highest potential for metastasis to the brain, ranking 15th in the frequency of occurrence among all malignant tumors – it is in third place in the incidence of intracerebral metastases. Modern methods of treatment of metastases of skin melanoma to the brain include neurosurgical treatment, radiation therapy and radiosurgery, antitumor drug therapy, including targeted therapy, immunotherapy and chemotherapy. The article discusses the indications for different methods of treatment, provides data on patient survival when using these methods of treatment alone or in combination. Additionally, a clinical case of long-term survival of a patient with skin melanoma with progression in the form of extra- and intracranial metastasis is discussed.Purpose. Evaluation of the result of using modern methods of antitumor treatment in real clinical practice in a patient with skin melanoma metastases in the brain. Materials and methods. On a clinical example, a possible sequence of an individual approach to the treatment of a patient with extracranial and intracerebral metastases of skin melanoma based on modern methods of treatment and examination is considered.Results. The use of modern methods of anticancer therapy has increased the overall survival and disease-free survival of patients with metastases of skin melanoma to the brain and reduces the need for neurosurgical interventions. As a confirmation of this, the life expectancy of the patient after the progression of skin melanoma in the form of metastases to the brain against the background of all the antitumor treatment carried out to date was 5.5 years, while neurosurgical treatment was not carried out at the request of the patient, although it was shown, but were used the possibilities of modern anticancer therapy, including sequential radiation therapy, targeted therapy and immunotherapy.Conclusion. Modern methods of anticancer therapy can significantly increase the survival rate of patients with melanoma brain metastases and individualize the treatment plan.
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