Allelic deletion on chromosome 17p13.3 in early ovarian cancer.
Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletions extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are see only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.
Phillips
N J
NJ
Department of Pathology, Saint Louis University School of Medicine, Missouri, USA.
Ziegler
M R
MR
Radford
D M
DM
Fair
K L
KL
Steinbrueck
T
T
Xynos
F P
FP
Donis-Keller
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm