Mechanism of cancer susceptibility associated with PCS (premature chromatid separation) genetic trait

癌症易感性与PCS（染色单体过早分离）遗传性状相关的机制

基本信息

批准号：
16590261
负责人：
IKEUCHI Tatsuro
金额：
$ 2.24万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590261/
关键词：
Premature chromatid separation PCS syndrome Chromosomal instability Aneuploid cells BUB1B gene Mitotic spindle checkpoint Wilms tumor Cancer prone genetic traait 早期染色分体解離 BUBR1遺伝子 BubR1 高発がん性遺伝形質分裂期チェックポイント染色体異数性トリソミー横紋筋肉

项目摘要

1. The PCS (premature chromatid separation) syndrome was established as a clinical entity (OMIM#176430) on the basis of our experiences in 7 Japanese families, being recognized to be a cancer-prone genetic trait due to the impairment of mitotic spindle checkpoint, or to the decreased expression of BUB1B-endoding protein (BubR1).2. The frequency of cells in PCS is the most important hallmark for diagnosis of PCS syndrome. Hypotonic treatment of cells at 37℃ for 20 min was found to be most suitable among the conditions tested for the detection of PCS in individuals with the homozygous or heterozygous for the PCS trait.3. Chromosomal and DNA polymorphic marker studies revealed that the tumors developing in PCS patients had uniparental (paternal) disomy (UPD) specifically for chromosome 11, suggesting that the increased dosage of imprinted genes such as paternally expressed IGF2 was primarily involved in tumor development.4. Molecular analysis of BUB1B (encoding BubR1 protein) was performed in 7 Japanese families with PCS syndrome. In all the families studied, monoallelic BUB1B mutations were found : a single-base deletion in 4 families, and a splice site mutation, a nonsence mutation, and a missene mutation in one family each. Further analysis of haplotypes in the secomd alleles, where no mutations were detected, is now in progress.5. Lymphoblastoid cell lines (LCLs) and fibroblasts derived from the two PCS patients and a number of LCLs from heterozygous carriers were established and stored.

1。PC（过早的染色体分离）综合征是作为临床实体E家族建立的，由于有丝分裂纺锤体检查点的损害或BUB1B dodododing蛋白的表达降低，因此被认为是一种容易发生癌症的遗传特征）.2 PC中的细胞频率是诊断NDROME的最重要的标志。 PCS特征的杂合子3。在所有研究的家庭中，都发现了PCS综合征：在4个家族中删除了单相关的BUB1B突变，一个位点突变，一个胡说八道的突变和对Secomd Alles中的单倍型的ER分析，未检测到妓女突变。现在正在进行中。5。

项目成果

期刊论文数量（46）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Two infants with homozygous premature chromatid separation trait

两名具有纯合早熟染色单体分离特征的婴儿

DOI：
发表时间：
2006
期刊：
American Journal of Human Genetics 77
影响因子：
0
作者：
Numabe;H.;Ikeuchi;T..;Kajii;T.;Kusakawa;I.;Kato;I.;Kosugi;S.
通讯作者：
S.

第13回臨床細胞遺伝学セミナーテキスト第1章 DNA,遺伝子,ゲノムと染色体

第十三届临床细胞遗传学研讨会正文第一章DNA、基因、基因组和染色体

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Machado RD;Aldred MA;James V;Harrison RE;Patel B;Schwalbe EC;Gruenig E;Janssen B;Koehler R;Seeger W;Eickelberg O;Olschewski H;Elliott CG;Glissmeyer E;Carlquist J;Kim M;Torbicki A;Fijalkowska A;Szewczyk G;Parma J;Abramowicz MJ;Galie N,;池内達郎(分担執筆)
通讯作者：
池内達郎(分担執筆)

Two modes of microsatellite instability in human cancer : differenttial connection of defective DNA mismatch repair to dinucleotide repeat instability

人类癌症中微卫星不稳定性的两种模式：有缺陷的DNA错配修复与二核苷酸重复不稳定性的不同联系