当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.

Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.

Abstract：

:High-resolution single nucleotide polymorphism genomic microarray (SNP-chip) is a useful tool to define gene dosage levels over the whole genome, allowing precise detection of deletions and duplications/amplifications of chromosomes in cancer cells. We found that this new technology can also identify breakpoints of chromosomes involved in unbalanced translocations, leading to identification of fusion genes. Using this technique, we found that the PAX5 gene was rearranged to a variety of partner genes including ETV6, FOXP1, AUTS2, and C20orf112 in pediatric acute lymphoblastic leukemia (ALL). The 3' end of the PAX5 gene was replaced by the partner gene. The PAX5 fusion products bound to PAX5 recognition sequences as strongly as wild-type PAX5 and suppressed its transcriptional activity in a dominant-negative fashion. In human B cell leukemia cells, binding of wild-type PAX5 to a regulatory region of BLK, one of the direct downstream target genes of PAX5, was diminished by expression of the PAX5-fusion protein, leading to repression of BLK. Expression of PAX5-fusion genes in murine bone marrow cells blocked development of mature B cells. PAX5-fusion proteins may contribute to leukemogenesis by blocking differentiation of hematopoietic cells into mature B cells. SNP-chip is a powerful tool to identify fusion genes in human cancers.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Kawamata N,Ogawa S,Zimmermann M,Niebuhr B,Stocking C,Sanada M,Hemminki K,Yamatomo G,Nannya Y,Koehler R,Flohr T,Miller CW,Harbott J,Ludwig WD,Stanulla M,Schrappe M,Bartram CR,Koeffler HP

doi

10.1073/pnas.0711039105

subject

Has Abstract

pub_date

2008-08-19 00:00:00

pages

11921-6

issue

33

eissn

0027-8424

issn

1091-6490

pii

0711039105

journal_volume

105

pub_type

杂志文章

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