Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian cancer.
Genetic changes have been shown to be important in determining the multistep progression of cancer. Allele loss studies and karyotypic analysis of epithelial ovarian tumours have indicated the presence of putative tumour suppressor genes on chromosomes 6, 11, 13, 17, 18, 22, and X. We have focused on chromosome arm 6q to identify the minimal region that may contain a putative tumour suppressor gene. Nineteen polymorphic microsatellite markers from 6q and one centromeric marker (D6S294) have been used to detect allele loss in 68 ovarian tumours (six benign, six borderline, and 56 with malignant histology). Allele loss was evaluated by separation of fluorescence labelled polymerase chain reaction-amplified products. Forty-six of fifty-six (82%) malignant tumours showed allele loss on 6q, whereas only four of 56 had lost all the markers tested. Forty-one of fifty-six (73%) malignant tumours showed allele loss at 6q26-27. The minimal region of allele loss was between markers D6S264 and D6S297 (3 cM), with maximal allele loss of 62% at D6S193 and 52% at D6S297. Three tumours showed loss of D6S193 only, while retaining flanking informative markers. Allele loss around 6q26-27 was observed in all histological types of epithelial ovarian cancer and did not correlate with any clinical factors. In addition, there was allele loss at ESR (56%) and D6S286 (47%), though a minimal region was not defined. Allele loss at 6q12-25 correlated significantly with endometrioid and mucinous ovarian malignant tumours (P = 0.01). The physical mapping of the region between D6S297 and D6S264 will allow the eventual identification of the putative tumour suppressor gene.
Cooke
I E
IE
Molecular Oncology Laboratories, Imperial Cancer Research Fund, Headington, Oxford, United Kingdom.
Shelling
A N
AN
Le Meuth
V G
VG
Charnock
M L
ML
Ganesan
T S
TS
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D017931:DNA Primers; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers