A candidate prostate cancer susceptibility gene at chromosome 17p

Citation
Sv. Tavtigian et al., A candidate prostate cancer susceptibility gene at chromosome 17p, NAT GENET, 27(2), 2001, pp. 172-180
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
1061-4036 → ACNP
Volume
27
Issue
2
Year of publication
2001
Pages
172 - 180
Database
ISI
SICI code
1061-4036(200102)27:2<172:ACPCSG>2.0.ZU;2-H
Abstract
It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees fr om Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined in terval, identifying a gene, ELAC2, harboring mutations (including a framesh ift and a nonconservative missense change) that segregate with prostate can cer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member o f an uncharacterized gene family predicted to encode a metal-dependent hydr olase domain that is conserved among eukaryotes, archaebacteria and eubacte ria. The gene product bears amino acid sequence similarity to two better un derstood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyaden ylation specificity factor (CPSF73).