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Molecular genetic analysis of high risk factors developing childhood cancers and its clinical applications

儿童癌症高危因素的分子遗传学分析及其临床应用

基本信息

批准号：
04454276
负责人：
BESSHO Fumio
金额：
$ 4.03万
依托单位：
University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

Several anti-oncogenes were studied for common childrhood cancers. Anti-oncogenes studied included p53 gene, p16/15 genes, Rb gene, DCC gene and NF1 gene. Generally, these genes tend to be mutated or deleted in cell lines more often than fresh tumor cells and in tumor cells of advanced stages and of relapsed cases. However, frequency of abnormalities of these genes varied among different tumor types. In spite of neural crest origin of both tumors, abnormalities of p53 genes were frequent seen in Ewing sarcoma but not in neuroblastoma. Abnormalities of p16/p15 genes were more frequently seen in common ALL antigen-positive acute lymphoblatic leukemia (ALL) without chromosome transloction, t (1 ; 19), than in ALL with this translocation. These abnormalies were also commn in T-ALL.Materials of non-Hodgkin lymphoma developed in 3 siblings and lung cancer in 11-year-old boy were negative for abnormalities of p53 gene. In these patients other tumor suppressor genes might be responsible for familial or rare development of their cancers.In addition to molecular study, epidemiological study was performed to find out familial clustering of common childhood cancers and constitutional factors affecting development of these cancers, using data of Japan Children's Cancer Registry (JCCR). We found that distribution of tumor types among family of children with cancer was different from that of general population. Brain tumor was more often seen in family of cancer, but colon cancer, lung cancer and cancer of bile duct were less often seen. Distribution of cancer types among parents and siblings whose family had cancers in 3 consecutive generations was different from cancer types of general population only in female and breast cancer and uterus cancer were more frequently seen.

研究了常见儿童癌症的几种抑癌基因。抑癌基因包括p53基因、p16/15基因、Rb基因、DCC基因和NF 1基因。通常，这些基因在细胞系中比在新鲜肿瘤细胞中以及在晚期和复发病例的肿瘤细胞中更常发生突变或缺失。然而，这些基因的异常频率在不同的肿瘤类型中有所不同。尽管两种肿瘤的神经嵴起源，p53基因的异常常见于尤文肉瘤，而不是在神经母细胞瘤。p16/p15基因异常在非t（1 ; 19）易位的ALL中发生率明显高于t（1 ; 19）易位的ALL。3例同胞非霍奇金淋巴瘤和1例11岁男孩肺癌标本p53基因均阴性。在这些患者中，其他肿瘤抑制基因可能是导致其癌症家族性或罕见发展的原因。除了分子研究外，还进行了流行病学研究，以了解常见儿童癌症的家族聚集性和影响这些癌症发展的体质因素，使用日本儿童癌症登记处（JCCR）的数据。发现肿瘤类型在儿童肿瘤家族中的分布与一般人群不同。肿瘤家族中以脑肿瘤多见，结肠癌、肺癌和胆管癌较少见。连续3代患癌的父母和兄弟姐妹的癌症类型分布与一般人群的癌症类型不同，仅女性癌症类型分布最多，乳腺癌和子宫癌更常见。