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恶性胶质瘤和髓母细胞瘤的细胞遗传学与分子遗传学

Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma.

作者信息

Bigner S H, Vogelstein B

机构信息

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.

出版信息

Brain Pathol. 1990 Sep;1(1):12-8. doi: 10.1111/j.1750-3639.1990.tb00633.x.

Abstract

Malignant gliomas and medulloblastomas which are the most common primary malignant brain tumours of adult and children, respectively, resemble other neurogenic tumours as they frequently contain gene amplification and show non-random loss of specific chromosomal regions. In gliomas the gene which is most often amplified, is the epidermal growth factor receptor gene. In many cases the gene is rearranged as well, producing abnormally small epidermal growth factor receptor proteins. More than 80% of tumours have lost chromosome 10 and losses of 9p13, 17p and 22 occur in subgroups of cases. 17p loss is associated with point mutations of the p53 gene, but the relevant genes in the other chromosomal regions remain to be identified. For medulloblastoma the most frequent chromosomal abnormality is i(17q). Whether or not p53 gene mutations are the targets of 17p losses in these tumours remains to be determined. Approximately 5% of medulloblastoma biopsies contain gene amplification, although the incidence in medulloblastoma cell lines is more than 80%. c-myc is the gene which is most frequently amplified in this tumour type. The relationship of these various molecular genetic abnormalities to the biology of the tumours and the course of the patients remains largely unexplored.

摘要

恶性胶质瘤和髓母细胞瘤分别是成人和儿童中最常见的原发性恶性脑肿瘤,它们与其他神经源性肿瘤相似,因为它们经常发生基因扩增并显示特定染色体区域的非随机丢失。在胶质瘤中,最常扩增的基因是表皮生长因子受体基因。在许多情况下,该基因也会发生重排,产生异常小的表皮生长因子受体蛋白。超过80%的肿瘤发生了10号染色体丢失,9p13、17p和22号染色体丢失发生在部分病例亚组中。17p丢失与p53基因的点突变有关,但其他染色体区域的相关基因仍有待确定。对于髓母细胞瘤,最常见的染色体异常是i(17q)。这些肿瘤中17p丢失的靶点是否是p53基因突变仍有待确定。大约5%的髓母细胞瘤活检样本存在基因扩增,尽管在髓母细胞瘤细胞系中的发生率超过80%。c-myc是这种肿瘤类型中最常扩增的基因。这些各种分子遗传异常与肿瘤生物学和患者病程之间的关系在很大程度上仍未得到探索。

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