Von Hippel-Lindau tumour suppressor gene is not involved in sporadic human breast cancer.
OBJECTIVE
Mutations of the von Hippel-Lindau (vhl) gene, as well as allelic loss at the gene region (3p25-26) have been described in sporadic cases of the tumour types participating in VHL disease, but also in cancers not associated with the syndrome. In this study, we attempted mutation analysis of the vhl gene, as well as detection of allelic loss at 3p25-26 in sporadic human breast cancer.


METHODS
Eighty-two tumour specimens were screened for loss of heterozygosity (LOH) at the vhl region, and compared to the adjacent, histologically normal tissue. Furthermore, mutations within the three exons of vhl in the same panel of tumours were detected using SSCP and heteroduplex analysis and direct sequencing.


RESULTS
To our knowledge this is the first mutational analysis reported for the vhl gene in breast cancer, however we failed to reveal any mutations in the specimens examined. All the cases were informative for at least one of the microsatellite markers tested, 24 (29.2%) exhibited LOH at 3p25-26. Clinical and pathological data were available for all tumours examined, however no significant correlations were encountered.


CONCLUSIONS
These results strongly indicate against a critical involvement of the tumour suppressor vhl in breast carcinogenesis.
Laboratory of Virology, Medical School, University of Crete, Heraklion, Greece.
G
G
Sourvinos
S
S
Miyakis
T L
TL
Liloglou
J K
JK
Field
D A
DA
Spandidos
D001940:Breast; D001943:Breast Neoplasms / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D005260:Female; D016153:Genes, Suppressor; D020180:Heteroduplex Analysis; D006801:Humans; D008025:Ligases; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human