Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors.
Allele losses from chromosome 17 are common in sporadic ovarian tumors. Previously, we reported high rates of LOH (up to 70%) from 17q25 at the marker THH59 in a bank of malignant ovarian tumors. We have extended this study to 70 tumors with 17 markers from the long arm of chromosome 17. In most cases, the data are consistent with whole chromosome loss, but we have identified a minimal region of deletion that is centered around 4 microsatellites with zero recombination at map position 106.9 cM. A P1/BAC contig across the region (approximately 200 kb) was constructed and used to determine the precise position and order of the microsatellites. The contig was shown to hybridize to 17q25 by fluorescence in situ hybridization analysis. The DNA sequence of the entire contig was determined and analyzed by BLAST searches. A 4-kb cDNA was subsequently identified with homology to the yeast, Drosophila and mammalian septin family of genes. We have designated this gene Ovarian/Breast (Ov/Br) septin. Two splice variants were demonstrated within the 200-kb contig, which differ only at exon 1. Within the contig, approximately 45% of the septin alpha transcript was identified and 38% of the septin beta transcript. The septins are a family of genes involved in cytokinesis and cell cycle control. Their known functions are consistent with the hypothesis that the human 17q25 septin gene is a candidate for the ovarian tumor suppressor gene.
Russell
S E
SE
Department of Oncology, The Queen's University of Belfast, Belfast City Hospital, United Kingdom. seh.russell@qub.ac.uk
McIlhatton
M A
MA
Burrows
J F
JF
Donaghy
P G
PG
Chanduloy
S
S
Petty
E M
EM
Kalikin
L M
LM
Church
S W
SW
McIlroy
S
S
Harkin
D P
DP
Keilty
G W
GW
Cranston
A N
AN
Weissenbach
J
J
Hickey
I
I
Johnston
P G
PG
D000595:Amino Acid Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D020451:Contig Mapping; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*; D058112:Septins; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C474315:SEPTIN9 protein, human; D058112:Septins