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Tissue‐specific cancer‐related serpin gene cluster at human chromosome band 3q26
Author(s) -
Chang WunShaing W.,
Chang NienTzu,
Lin ShengChieh,
Wu ChengWen,
Wu Felicia Y.H.
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(2000)9999:9999<::aid-gcc1029>3.0.co;2-a
Subject(s) - serpin , biology , gene , genetics , intron , exon , gene cluster , microbiology and biotechnology
Approximately one quarter of the identified human serpin genes are cancer‐related and clustered mainly at two distinct loci: 6p25 and 18q21. We have studied a novel serpin gene cluster at 3q26 containing at least two recently identified members: the pancreas‐specific protease inhibitor, pancpin ( PI14 ), and the brain‐associated protease inhibitor, neuroserpin ( PI12 ). In this, unlike a previous study, both PI14 and PI12 at 3q26 were found to consist of 9 exons and 8 introns and to share a perfectly conserved gene organization whose pattern is very different from that of the ov‐serpin family. This distinct pattern appears identical in the genomic structures of human plasminogen activator inhibitor‐1 ( PAI1 ) at 7q21 and protease nexin 1 ( PI7 ) at 2q33–35, confirming that these four genes in three different chromosomes form a discrete subset within the serpin superfamily. As in the other three members whose gene expression is altered during tumorigenesis, PI12 expression was found to be down‐regulated in tumor brain tissues and in two brain cancer cell lines: U‐87 MG and H4. By screening genomic libraries, we isolated two overlapping clones showing that the marker SGC32223 (centromere) is located within intron F of PI12 and the marker WI‐10077 (telomere) is located downstream of the 3′‐flanking region of PI14 . This finding indicates that the distance between human PI14 and PI12 is ∼100 kb, and hence we speculate that other tissue‐specific cancer‐related serpin genes are likely to reside within this 3q26.1 cluster region. © 2000 Wiley‐Liss, Inc.