A candidate prostate cancer susceptibility gene at chromosome 17p.
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 from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).
Tavtigian
S V
SV
Myriad Genetics, Inc., Salt Lake City, Utah, USA. seant@myriad.com
Simard
J
J
Teng
D H
DH
Abtin
V
V
Baumgard
M
M
Beck
A
A
Camp
N J
NJ
Carillo
A R
AR
Chen
Y
Y
Dayananth
P
P
Desrochers
M
M
Dumont
M
M
Farnham
J M
JM
Frank
D
D
Frye
C
C
Ghaffari
S
S
Gupte
J S
JS
Hu
R
R
Iliev
D
D
Janecki
T
T
Kort
E N
EN
Laity
K E
KE
Leavitt
A
A
Leblanc
G
G
McArthur-Morrison
J
J
Pederson
A
A
Penn
B
B
Peterson
K T
KT
Reid
J E
JE
Richards
S
S
Schroeder
M
M
Smith
R
R
Snyder
S C
SC
Swedlund
B
B
Swensen
J
J
Thomas
A
A
Tranchant
M
M
Woodland
A M
AM
Labrie
F
F
Skolnick
M H
MH
Neuhausen
S
S
Rommens
J
J
Cannon-Albright
L A
LA
D000595:Amino Acid Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003001:Cloning, Molecular / Q000379:methods; D018076:DNA, Complementary / Q000235:genetics; D018703:Founder Effect; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014589:Utah
D018076:DNA, Complementary; C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger