Refinement of an ovarian cancer tumour suppressor gene locus on chromosome arm 22q and mutation analysis of CYP2D6, SREBP2 and NAGA.
Loss of heterozygosity on chromosome 22q was detected in 53% of 123 ovarian carcinomas, suggesting the presence of at least one tumour suppressor gene. We have refined the location of one possible tumour suppressor gene to the region between the microsatellite markers D22S299 and CYP2D. Located within this region are the genes SREBP2 (sterol regulatory element binding protein 2) and NAGA (N-acetyl-alpha-D-galactosaminidase). Investigation of the coding exons of these genes by single stranded conformational polymorphism/heteroduplex analysis failed to identify any somatic genetic alterations in 57 ovarian tumours which exhibited LOH on 22q13. The CYP2D gene locus straddles the distal boundary of the candidate region. Germline variants of the active CYP2D6 gene with differing abilities to metabolise specific substrates have been implicated in the development of various cancers. Comparison of the frequency of the two common germline mutations among 258 ovarian tumours and 231 non-cancer controls did not reveal any significant differences between the two groups. This suggests that the known polymorphic variants of CYP2D6 are not involved in ovarian cancer predisposition. We also conclude that neither NAGA nor SREBP2 are likely to be mutated in ovarian carcinomas.
Bryan
E J
EJ
VBCRC, Cancer Genetics Laboratory, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia.
Thomas
N A
NA
Palmer
K
K
Dawson
E
E
Englefield
P
P
Campbell
I G
IG
D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005838:Genotype; D006596:Hexosaminidases / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics; D048809:alpha-N-Acetylgalactosaminidase
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D019389:Cytochrome P-450 CYP2D6; D006596:Hexosaminidases; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase