Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22.
Monosomy 7 and deletions of 7q are recurring leukemia-associated cytogenetic abnormalities that correlate with adverse outcomes in children and adults. We describe a 2.52-Mb genomic DNA contig that spans a commonly deleted segment of chromosome band 7q22 identified in myeloid malignancies. This interval currently includes 14 genes, 19 predicted genes, and 5 predicted pseudogenes. We have extensively characterized the FBXL13, NAPE-PLD, and SVH genes as candidate myeloid tumor suppressors. FBXL13 encodes a novel F-box protein, SVHis a member of a gene family that contains Armadillo-like repeats, and NAPE-PLD encodes a phospholipase D-type phosphodiesterase. Analysis of a panel of leukemia specimens with monosomy 7 did not reveal mutations in these or in the candidate genes LRRC17, PRO1598, and SRPK2. This fully sequenced and annotated contig provides a resource for candidate myeloid tumor suppressor gene discovery.
Curtiss
Nicole P
NP
Department of Pediatrics, University of California at San Francisco, 513 Parnassus Avenue, HSE 302, San Francisco, CA 94143, USA.
Bonifas
Jeannette M
JM
Lauchle
Jennifer O
JO
Balkman
Jason D
JD
Kratz
Christian P
CP
Emerling
Brooke M
BM
Green
Eric D
ED
Le Beau
Michelle M
MM
Shannon
Kevin M
KM
D001483:Base Sequence; D015152:Blotting, Northern; D019046:Bone Marrow Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003001:Cloning, Molecular; D019295:Computational Biology; D020451:Contig Mapping; D018076:DNA, Complementary / Q000235:genetics; D030561:Databases, Nucleic Acid; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*
C476102:ARMC10 protein, human; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D015534:Trans-Activators