Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23.
Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. Most cases ( approximately 70%) identified and characterized to date are associated with dominantly inherited germ line mutations in the tumor suppressor gene TP53 (p53) in chromosome 17p13.1. In a subset of non-p53 patients with LFS, CHEK2 in chromosome 22q11 has been identified as another predisposing locus. Studying a series of non-p53 LFS kindred, we have shown that there is additional genetic heterogeneity in LFS kindred with inherited predisposition at loci other than p53 or CHEK2. Using a genome-wide scan for linkage with complementing parametric and nonparametric analysis methods, we identified linkage to a region of approximately 4 cM in chromosome 1q23, a genomic region not previously implicated in this disease. Identification ofa third predisposing gene and its underlying mutation(s) should provide insight into other genetic events that predispose to the genesis of the diverse tumor types associated with LFS and its variants.
Bachinski
Linda L
LL
Section of Cancer Genetics, Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Olufemi
Shodimu-Emmanuel
SE
Zhou
Xiaojun
X
Wu
Chih-Chieh
CC
Yip
Linwah
L
Shete
Sanjay
S
Lozano
Guillermina
G
Amos
Christopher I
CI
Strong
Louise C
LC
Krahe
Ralf
R
D064447:Checkpoint Kinase 2; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases