Correlation of chromosomal imbalances by comparative genomic hybridization and expression of EGFR, PTEN, p53, and MIB-1 in diffuse gliomas

The histological subclassification of gliomas is increasingly assisted by the underlying molecular genetics which has major importance in guiding clinical management of the disease. However, the assessment of several molecular events for improving clinical care remains a challenge. Herein, we report on comparative genomic hybridization (CGH) and immunohistochemical (IHC) assessment of EGFR, PTEN, p53, and MIB-1 expression in 13 oligodendrogliomas (10 WHO grade II, 3 WHO grade III), one oligoastrocytoma (WHO grade III) and 23 high-grade astrocytomas Q WHO grade III, 20 glioblastoma multiforme). The most frequent imbalances in oligodendroglial tumors including the oligoastrocytic case were, in decreasing order of frequency, +7q, -1p, and -4q and in astrocytomas +7q, -10q, +7p, -9p, -10p, +20q, and +20p. Some individual imbalances were associated with increasing numbers of chromosomal changes, that were +7q in both oligodendrogliomas and astrocytomas, and -9p, -10q, +20p, and +20q in astrocytomas. The markers p53 and MIB-1 were significantly higher expressed in astrocytomas than in oligodendrogliomas and expression levels of p53 and EGFR were inversely associated within the astrocytic group. In addition, p53 overexpression correlated positively with +7q and negatively with -1p in the oligodendroglial group whereas EGFR overexpression correlated positively with -1p in the oligodendroglial and positively with +7p and -10p in the astrocytic group. Short overall survival was significantly associated with +7p and -10q in astrocytomas. Collectively, these results contribute to the increasing clinical relevance of assessing tumor biological markers in gliomas

Определение объема вычислительных экспериментов при решении задач оптимизационного синтеза динамических систем методом ПЛП-поиска

Даются рекомендации по выбору необходимого числа машинных экспериментов при решении конкретных задач исследования и оптимального проектирования методом ПЛП-поиска, позволяющего осуществлять глобальный квазиравномерный просмотр заданной области варьируемых параметров и применить формальные оценки из математической статистики.Recommendations about the choice of necessary number of machine experiments at the solution of specific objectives of a research and optimum design are made by method of the PLP-search allowing to carry out global quasi uniform viewing of the set area of the varied parameters and to apply formal estimates from mathematical statistics

Устройство автоматического регулирования жидкости

Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 c-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 × 10-5), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003). Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Maximum Likelihood Estimation of Oncogenetic Tree Models

We present a new approach for modelling the occurrence of genetic changes in human tumours over time. In solid tumours, data on genetic alterations are usually only available at a single point in time, allowing no direct insight into the sequential order of genetic events. In our approach, genetic tumour development and progression is assumed to follow a probabilistic tree model. We show how maximum likelihood estimation can be used to reconstruct a tree model for the genetic evolution of a given tumour type. We illustrate the use of the proposed method by applying it to cytogenetic data from 173 cases of clear cell renal cell carcinoma, arriving at a model for the karyotypic evolution of this tumour